PARG-deficient tumor cells have an increased dependence on EXO1/FEN1-mediated DNA repair

Targeting poly(ADP-ribose) glycohydrolase (PARG) is currently explored as a therapeutic approach to treat various cancer types, but we have a poor understanding of the specific genetic vulnerabilities that would make cancer cells susceptible to such a tailored therapy. Moreover, the identification o...

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Veröffentlicht in:The EMBO journal Jg. 43; H. 6; S. 1015 - 1042
Hauptverfasser: Andronikou, Christina, Burdova, Kamila, Dibitetto, Diego, Lieftink, Cor, Malzer, Elke, Kuiken, Hendrik J, Gogola, Ewa, Ray Chaudhuri, Arnab, Beijersbergen, Roderick L, Hanzlikova, Hana, Jonkers, Jos, Rottenberg, Sven
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 15.03.2024
Schlagworte:
Biomedical and Life Sciences
DNA Damage
DNA Repair
DNA Repair Enzymes - genetics
EMBO03
EMBO13
EMBO31
Exodeoxyribonucleases - genetics
Flap Endonucleases - genetics
Flap Endonucleases - metabolism
Flap Endonucleases - therapeutic use
Glycoside Hydrolases - genetics
Glycoside Hydrolases - metabolism
Humans
Life Sciences
Neoplasms - drug therapy
Neoplasms - genetics
Poly(ADP-ribose) Polymerase Inhibitors - pharmacology
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
FEN1
PARG
BRCA2
EXO1
DNA Repair
ISSN:1460-2075, 0261-4189, 1460-2075
Online-Zugang:Volltext
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Abstract Targeting poly(ADP-ribose) glycohydrolase (PARG) is currently explored as a therapeutic approach to treat various cancer types, but we have a poor understanding of the specific genetic vulnerabilities that would make cancer cells susceptible to such a tailored therapy. Moreover, the identification of such vulnerabilities is of interest for targeting BRCA2;p53-deficient tumors that have acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPi) through loss of PARG expression. Here, by performing whole-genome CRISPR/Cas9 drop-out screens, we identify various genes involved in DNA repair to be essential for the survival of PARG;BRCA2;p53-deficient cells. In particular, our findings reveal EXO1 and FEN1 as major synthetic lethal interactors of PARG loss. We provide evidence for compromised replication fork progression, DNA single-strand break repair, and Okazaki fragment processing in PARG;BRCA2;p53-deficient cells, alterations that exacerbate the effects of EXO1/FEN1 inhibition and become lethal in this context. Since this sensitivity is dependent on BRCA2 defects, we propose to target EXO1/FEN1 in PARPi-resistant tumors that have lost PARG activity. Moreover, EXO1/FEN1 targeting may be a useful strategy for enhancing the effect of PARG inhibitors in homologous recombination-deficient tumors. Synopsis Targeting poly(ADP-ribose) glycohydrolase (PARG) is being explored as anti-cancer therapeutic strategy, and PARG loss may also contribute to resistance to PARP inhibitor (PARPi) treatment. This study provides insights into specific vulnerabilities that can render homologous-recombination (HR)-deficient tumors susceptible to the loss of PARG activity. Impaired de-PARylation in PARG-deficient cells affects the repair of single-strand breaks (SSBs) and processing of unligated Okazaki fragments. Genome-wide CRISPR/Cas9 screens reveal EXO1 and FEN1 as critical factors in cells deficient for PARG and BRCA2. Inhibition of EXO1/FEN1 in PARG;BRCA2-deficient cells results in unresolved Okazaki fragments, which persist as single-strand DNA (ssDNA) gaps. Persistent ssDNA gaps become specifically lethal to HR-deficient cells when converted into double-strand breaks (DSBs) upon replication. Genome-wide loss-of-function screens reveal DNA repair genes essential in HR-defective cells lacking PARG, suggesting ways for therapeutically exploiting PARG inhibitors and targeting PARPi-resistant tumors.
AbstractList Targeting poly(ADP-ribose) glycohydrolase (PARG) is currently explored as a therapeutic approach to treat various cancer types, but we have a poor understanding of the specific genetic vulnerabilities that would make cancer cells susceptible to such a tailored therapy. Moreover, the identification of such vulnerabilities is of interest for targeting BRCA2;p53-deficient tumors that have acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPi) through loss of PARG expression. Here, by performing whole-genome CRISPR/Cas9 drop-out screens, we identify various genes involved in DNA repair to be essential for the survival of PARG;BRCA2;p53-deficient cells. In particular, our findings reveal EXO1 and FEN1 as major synthetic lethal interactors of PARG loss. We provide evidence for compromised replication fork progression, DNA single-strand break repair, and Okazaki fragment processing in PARG;BRCA2;p53-deficient cells, alterations that exacerbate the effects of EXO1/FEN1 inhibition and become lethal in this context. Since this sensitivity is dependent on BRCA2 defects, we propose to target EXO1/FEN1 in PARPi-resistant tumors that have lost PARG activity. Moreover, EXO1/FEN1 targeting may be a useful strategy for enhancing the effect of PARG inhibitors in homologous recombination-deficient tumors. Targeting poly(ADP-ribose) glycohydrolase (PARG) is being explored as anti-cancer therapeutic strategy, and PARG loss may also contribute to resistance to PARP inhibitor (PARPi) treatment. This study provides insights into specific vulnerabilities that can render homologous-recombination (HR)-deficient tumors susceptible to the loss of PARG activity. Impaired de-PARylation in PARG-deficient cells affects the repair of single-strand breaks (SSBs) and processing of unligated Okazaki fragments.Genome-wide CRISPR/Cas9 screens reveal EXO1 and FEN1 as critical factors in cells deficient for PARG and BRCA2.Inhibition of EXO1/FEN1 in PARG;BRCA2-deficient cells results in unresolved Okazaki fragments, which persist as single-strand DNA (ssDNA) gaps.Persistent ssDNA gaps become specifically lethal to HR-deficient cells when converted into double-strand breaks (DSBs) upon replication. Genome-wide loss-of-function screens reveal DNA repair genes essential in HR-defective cells lacking PARG, suggesting ways for therapeutically exploiting PARG inhibitors and targeting PARPi-resistant tumors.
Targeting poly(ADP-ribose) glycohydrolase (PARG) is currently explored as a therapeutic approach to treat various cancer types, but we have a poor understanding of the specific genetic vulnerabilities that would make cancer cells susceptible to such a tailored therapy. Moreover, the identification of such vulnerabilities is of interest for targeting BRCA2;p53-deficient tumors that have acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPi) through loss of PARG expression. Here, by performing whole-genome CRISPR/Cas9 drop-out screens, we identify various genes involved in DNA repair to be essential for the survival of PARG;BRCA2;p53-deficient cells. In particular, our findings reveal EXO1 and FEN1 as major synthetic lethal interactors of PARG loss. We provide evidence for compromised replication fork progression, DNA single-strand break repair, and Okazaki fragment processing in PARG;BRCA2;p53-deficient cells, alterations that exacerbate the effects of EXO1/FEN1 inhibition and become lethal in this context. Since this sensitivity is dependent on BRCA2 defects, we propose to target EXO1/FEN1 in PARPi-resistant tumors that have lost PARG activity. Moreover, EXO1/FEN1 targeting may be a useful strategy for enhancing the effect of PARG inhibitors in homologous recombination-deficient tumors. Synopsis Targeting poly(ADP-ribose) glycohydrolase (PARG) is being explored as anti-cancer therapeutic strategy, and PARG loss may also contribute to resistance to PARP inhibitor (PARPi) treatment. This study provides insights into specific vulnerabilities that can render homologous-recombination (HR)-deficient tumors susceptible to the loss of PARG activity. Impaired de-PARylation in PARG-deficient cells affects the repair of single-strand breaks (SSBs) and processing of unligated Okazaki fragments. Genome-wide CRISPR/Cas9 screens reveal EXO1 and FEN1 as critical factors in cells deficient for PARG and BRCA2. Inhibition of EXO1/FEN1 in PARG;BRCA2-deficient cells results in unresolved Okazaki fragments, which persist as single-strand DNA (ssDNA) gaps. Persistent ssDNA gaps become specifically lethal to HR-deficient cells when converted into double-strand breaks (DSBs) upon replication. Genome-wide loss-of-function screens reveal DNA repair genes essential in HR-defective cells lacking PARG, suggesting ways for therapeutically exploiting PARG inhibitors and targeting PARPi-resistant tumors.
Targeting poly(ADP-ribose) glycohydrolase (PARG) is currently explored as a therapeutic approach to treat various cancer types, but we have a poor understanding of the specific genetic vulnerabilities that would make cancer cells susceptible to such a tailored therapy. Moreover, the identification of such vulnerabilities is of interest for targeting BRCA2;p53-deficient tumors that have acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPi) through loss of PARG expression. Here, by performing whole-genome CRISPR/Cas9 drop-out screens, we identify various genes involved in DNA repair to be essential for the survival of PARG;BRCA2;p53-deficient cells. In particular, our findings reveal EXO1 and FEN1 as major synthetic lethal interactors of PARG loss. We provide evidence for compromised replication fork progression, DNA single-strand break repair, and Okazaki fragment processing in PARG;BRCA2;p53-deficient cells, alterations that exacerbate the effects of EXO1/FEN1 inhibition and become lethal in this context. Since this sensitivity is dependent on BRCA2 defects, we propose to target EXO1/FEN1 in PARPi-resistant tumors that have lost PARG activity. Moreover, EXO1/FEN1 targeting may be a useful strategy for enhancing the effect of PARG inhibitors in homologous recombination-deficient tumors.Targeting poly(ADP-ribose) glycohydrolase (PARG) is currently explored as a therapeutic approach to treat various cancer types, but we have a poor understanding of the specific genetic vulnerabilities that would make cancer cells susceptible to such a tailored therapy. Moreover, the identification of such vulnerabilities is of interest for targeting BRCA2;p53-deficient tumors that have acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPi) through loss of PARG expression. Here, by performing whole-genome CRISPR/Cas9 drop-out screens, we identify various genes involved in DNA repair to be essential for the survival of PARG;BRCA2;p53-deficient cells. In particular, our findings reveal EXO1 and FEN1 as major synthetic lethal interactors of PARG loss. We provide evidence for compromised replication fork progression, DNA single-strand break repair, and Okazaki fragment processing in PARG;BRCA2;p53-deficient cells, alterations that exacerbate the effects of EXO1/FEN1 inhibition and become lethal in this context. Since this sensitivity is dependent on BRCA2 defects, we propose to target EXO1/FEN1 in PARPi-resistant tumors that have lost PARG activity. Moreover, EXO1/FEN1 targeting may be a useful strategy for enhancing the effect of PARG inhibitors in homologous recombination-deficient tumors.
Targeting poly(ADP-ribose) glycohydrolase (PARG) is currently explored as a therapeutic approach to treat various cancer types, but we have a poor understanding of the specific genetic vulnerabilities that would make cancer cells susceptible to such a tailored therapy. Moreover, the identification of such vulnerabilities is of interest for targeting BRCA2;p53-deficient tumors that have acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPi) through loss of PARG expression. Here, by performing whole-genome CRISPR/Cas9 drop-out screens, we identify various genes involved in DNA repair to be essential for the survival of PARG;BRCA2;p53-deficient cells. In particular, our findings reveal EXO1 and FEN1 as major synthetic lethal interactors of PARG loss. We provide evidence for compromised replication fork progression, DNA single-strand break repair, and Okazaki fragment processing in PARG;BRCA2;p53-deficient cells, alterations that exacerbate the effects of EXO1/FEN1 inhibition and become lethal in this context. Since this sensitivity is dependent on BRCA2 defects, we propose to target EXO1/FEN1 in PARPi-resistant tumors that have lost PARG activity. Moreover, EXO1/FEN1 targeting may be a useful strategy for enhancing the effect of PARG inhibitors in homologous recombination-deficient tumors.
Author Malzer, Elke
Kuiken, Hendrik J
Andronikou, Christina
Jonkers, Jos
Rottenberg, Sven
Gogola, Ewa
Dibitetto, Diego
Hanzlikova, Hana
Ray Chaudhuri, Arnab
Burdova, Kamila
Beijersbergen, Roderick L
Lieftink, Cor
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/38360994$$D View this record in MEDLINE/PubMed
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Cites_doi 10.1021/acschembio.6b00609
10.1038/s41467-020-17069-9
10.1128/MCB.01077-14
10.1158/2159-8290.CD-17-0734
10.1128/MCB.02248-06
10.1038/s41467-017-01180-5
10.1002/bies.20085
10.1158/1078-0432.CCR-07-4953
10.1038/nrm.2017.53
10.1038/nature03445
10.7554/eLife.28533
10.1371/journal.pone.0018618
10.1083/jcb.201402114
10.1016/j.annonc.2020.10.470
10.1371/journal.pone.0179278
10.1158/0008-5472.CAN-12-2753
10.1371/journal.pone.0010089
10.1016/j.molcel.2023.12.039
10.1101/gad.334516.119
10.1038/nmeth.3047
10.1038/ncomms1889
10.1038/s41594-022-00747-1
10.3389/fcell.2020.564601
10.1093/nar/gku936
10.1126/sciadv.aav4340
10.1038/nature03443
10.1126/scitranslmed.aaf9246
10.1038/s41467-019-08859-x
10.1021/acs.jmedchem.8b01407
10.1101/gr.191452.115
10.3390/ijms23158412
10.1038/nsmb.2305
10.1038/emboj.2013.51
10.1091/mbc.E18-10-0650
10.1186/s12859-017-1934-z
10.1038/nature06548
10.1146/annurev-cancerbio-030617-050232
10.1038/s41571-021-00532-x
10.1038/nchembio.2148
10.1101/gad.1331805
10.1093/jnci/djw148
10.1038/ncomms3164
10.1242/jcs.128272
10.1073/pnas.131009198
10.1074/jbc.M510290200
10.1016/j.pbiomolbio.2021.01.004
10.1158/1078-0432.CCR-13-1262
10.1016/bs.mie.2017.03.019
10.1146/annurev-cancerbio-030617-050502
10.1002/path.4140
10.1124/jpet.113.210146
10.1016/j.ccell.2018.05.008
10.1038/nature10404
10.1038/ng747
10.1016/j.molcel.2018.04.016
10.1016/j.celrep.2016.09.079
10.1016/j.dnarep.2018.08.021
10.1038/76095
10.1016/j.dnarep.2015.04.008
10.1016/S0076-6879(05)09024-5
10.1038/sj.embor.7400774
10.1016/j.celrep.2023.112538
10.1007/978-1-4939-6337-9_5
10.1042/BSR20150058
10.1002/1878-0261.13224
10.1038/nature06633
10.1016/j.molcel.2018.06.004
10.1016/j.molcel.2018.12.008
10.1016/j.ccell.2019.02.004
10.1093/nar/gky1131
10.1007/s00412-013-0442-9
10.1038/cddiscovery.2016.11
10.1158/2159-8290.CD-18-0715
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IsDoiOpenAccess true
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Issue 6
Keywords FEN1
PARG
BRCA2
EXO1
DNA Repair
Language English
License 2024. The Author(s).
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References Ray Chaudhuri, Nussenzweig (CR58) 2017; 18
Pascal, Ellenberger (CR52) 2015; 32
Houl, Ye, Brosey, Balapiti-Modarage, Namjoshi, Bacolla, Laverty, Walker, Pourfarjam, Warden (CR30) 2019; 10
Rueden, Schindelin, Hiner, DeZonia, Walter, Arena, Eliceiri (CR60) 2017; 18
Tzelepis, Koike-Yusa, De Braekeleer, Li, Metzakopian, Dovey, Mupo, Grinkevich, Li, Mazan (CR69) 2016; 17
Vaitsiankova, Burdova, Sobol, Gautam, Benada, Hanzlikova, Caldecott (CR71) 2022; 29
Oka, Kato, Moss (CR50) 2006; 281
Waszkowycz, Smith, McGonagle, Jordan, Acton, Fairweather, Griffiths, Hamilton, Hamilton, Hitchin (CR73) 2018; 61
Pommier, O’Connor, de Bono (CR55) 2016; 8
Tallis, Morra, Barkauskaite, Ahel (CR67) 2014; 123
CR38
Pillay, Tighe, Nelson, Littler, Coulson-Gilmer, Bah, Golder, Bakker, Spierings, James (CR54) 2019; 35
CR77
Cortés-Ledesma, Aguilera (CR13) 2006; 7
Murai, Zhang, Morris, Ji, Takeda, Doroshow, Pommier (CR48) 2014; 349
Lin, Harrell, Oza, Oaknin, Ray-coquard, Tinker, Helman, Radke, Say, Vo (CR43) 2019; 9
Leung (CR41) 2014; 205
Lupo, Trusolino (CR45) 2014; 1846
D’Andrea (CR14) 2018; 71
Murata, Kong, Moncada, Chen, Imamura, Wang, Berns, Yokomori, Digman (CR49) 2019; 30
Chen, Yu (CR12) 2019; 5
Jastrzebski, Evers, Beijersbergen (CR32) 2016; 1470
Love, Huber, Anders (CR44) 2014; 15
Ray Chaudhuri, Ahuja, Herrador, Lopes (CR57) 2015; 35
Amé, Spenlehauer, de Murcia (CR1) 2004; 26
Hanzlikova, Prokhorova, Krejcikova, Cihlarova, Kalasova, Kubovciak, Sachova, Hailstone, Brazina, Ghosh (CR29) 2020; 11
Slade, Dunstan, Barkauskaite, Weston, Lafite, Dixon, Ahel, Leys, Ahel (CR65) 2011; 477
Dias, Moser, Ganesan, Jonkers (CR15) 2021; 18
Gogola, Duarte, de Ruiter, Wiegant, Schmid, de Bruijn, James, Guerrero Llobet, Vis, Annunziato (CR26) 2018; 33
Lemaçon, Jackson, Quinet, Brickner, Li, Yazinski, You, Ira, Zou, Mosammaparast (CR40) 2017; 8
Tobalina, Armenia, Irving, O’Connor, Forment (CR68) 2021; 32
O’Sullivan, Tedim Ferreira, Gagné, Sharma, Hendzel, Masson, Poirier (CR51) 2019; 10
ter Brugge, Kristel, van der Burg, Boon, de Maaker, Lips, Mulder, de Ruiter, Moutinho, Gevensleben (CR9) 2016; 108
Xu, Sun, Liu, Guo, Liu, Jiang, Zou, Gong, Tischfield, Shao (CR75) 2011; 6
Evers, Drost, Schut, De Bruin, Van Burg, Der, Derksen, Holstege, Liu, Van Drunen, Beverloo (CR20) 2008; 14
Sakai, Swisher, Karlan, Agarwal, Higgins, Friedman, Villegas, Jacquemont, Farrugia, Couch (CR61) 2008; 451
Sharifi, Morra, Appel, Tallis, Chioza, Jankevicius, Simpson, Matic, Ozkan, Golia (CR63) 2013; 32
Quinet, Carvajal-Maldonado, Lemacon, Vindigni (CR56) 2017; 591
Li, Xu, Xiao, Cong, Love, Zhang, Irizarry, Liu, Brown, Liu (CR42) 2014; 15
Bhin, Paes Dias, Gogola, Rolfs, Piersma, de Bruijn, de Ruiter, van den Broek, Duarte, Sol (CR6) 2023; 42
Jonkers, Meuwissen, van der Gulden, Peterse, van der Valk, Berns (CR33) 2001; 29
Szklarczyk, Gable, Lyon, Junge, Wyder, Huerta-cepas, Simonovic, Doncheva, Morris, Bork (CR66) 2019; 47
Kuzminov (CR39) 2001; 98
Dunstan, Barkauskaite, Lafite, Knezevic, Brassington, Ahel, Hergenrother, Leys, Ahel (CR18) 2012; 3
Ward, McHugh, Durant (CR72) 2017; 12
Rose, Burgess, O’Byrne, Richard, Bolderson (CR59) 2020; 8
Chen, Feng, Lim, Kass, Jasin (CR11) 2018; 2
Follenzi, Ailles, Bakovic, Geuna, Naldini (CR24) 2000; 25
Wei, Nakajima, Hsieh, Kanno, Masutani, Levine, Yasui, Lan (CR74) 2013; 126
Kim, Zhang, Kraus (CR37) 2005; 19
Ding, Zhang, Wang, Zhang, Gao, Yin, Li, Li, Chen (CR16) 2016; 2
Edwards, Brough, Lord, Natrajan, Vatcheva, Levine, Boyd, Reis-Filho, Ashworth (CR19) 2008; 451
Hanzlikova, Kalasova, Demin, Pennicott, Cihlarova, Caldecott (CR28) 2018; 71
Kim, Nam (CR35) 2022; 23
Slade (CR64) 2020; 34
Kim, Kiefer, Ho, Stegeman, Classen, Tainer, Ellenberger (CR36) 2012; 19
Ang, Gourley, Powell, High, Shapira-Frommer, Castonguay, De Greve, Atkinson, Yap, Sandhu (CR2) 2013; 19
Barber, Sandhu, Chen, Campbell, Kozarewa, Fenwick, Assiotis, Rodrigues, Reis Filho, Moreno (CR3) 2013; 229
Utani, Kohno, Okamoto, Shimizu (CR70) 2010; 5
Keijzers, Bohr, Rasmussen (CR34) 2015; 35
Exell, Thompson, Finger, Shaw, Debreczeni, Ward, McWhirter, Siöberg, Molina, Abbott (CR21) 2016; 12
Bryant, Schultz, Thomas, Parker, Flower, Lopez, Kyle, Meuth, Curtin, Helleday (CR10) 2005; 434
Murai, Huang, Das, Renaud, Zhang, Doroshow, Ji, Takeda, Pommier (CR47) 2012; 72
Sanjana, Shalem, Zhang (CR62) 2014; 11
Barkauskaite, Brassington, Tan, Warwicker, Dunstan, Banos, Lafite, Ahel, Mitchison, Ahel (CR4) 2013; 4
Brinkman, Chen, de Haas, Holland, Akhtar, van Steensel (CR8) 2018; 70
Fisher, Hochegger, Takeda, Caldecott (CR23) 2007; 27
Pillay, Brady, Dey, Morgan, Taylor (CR53) 2021; 163
Baxter, Zatreanu, Pettitt, Lord (CR5) 2022; 16
Domchek (CR17) 2017; 7
Fontana, Bonfiglio, Palazzo, Bartlett, Matic, Ahel (CR25) 2017; 6
Mengwasser, Adeyemi, Leng, Choi, Clairmont, D’Andrea, Elledge (CR46) 2019; 73
Brinkman, Chen, Amendola, Van Steensel (CR7) 2014; 42
Xu, Xiao, Chen, Li, Meyer, Wu, Wu, Cong, Zhang, Liu (CR76) 2015; 25
Gogola, Rottenberg, Jonkers (CR27) 2017; 3
James, Smith, Jordan, Fairweather, Gri, Hamilton, Hitchin, Hutton, Jones, Kelly (CR31) 2016; 11
Farmer, McCabe, Lord, Tutt, Johnson, Richardson, Santarosa, Dillon, Hickson, Knights (CR22) 2005; 434
B Xu (43_CR75) 2011; 6
E Gogola (43_CR26) 2018; 33
AKL Leung (43_CR41) 2014; 205
L Tobalina (43_CR68) 2021; 32
A Kuzminov (43_CR39) 2001; 98
DI James (43_CR31) 2016; 11
L Wei (43_CR74) 2013; 126
K Utani (43_CR70) 2010; 5
A Vaitsiankova (43_CR71) 2022; 29
H Hanzlikova (43_CR29) 2020; 11
D Slade (43_CR64) 2020; 34
NE Sanjana (43_CR62) 2014; 11
H Hanzlikova (43_CR28) 2018; 71
LJ Barber (43_CR3) 2013; 229
JH Houl (43_CR30) 2019; 10
N Pillay (43_CR53) 2021; 163
H Xu (43_CR76) 2015; 25
R Sharifi (43_CR63) 2013; 32
S-H Chen (43_CR12) 2019; 5
A Quinet (43_CR56) 2017; 591
MS Dunstan (43_CR18) 2012; 3
N Pillay (43_CR54) 2019; 35
H Farmer (43_CR22) 2005; 434
J-C Amé (43_CR1) 2004; 26
SL Edwards (43_CR19) 2008; 451
EK Brinkman (43_CR8) 2018; 70
M Rose (43_CR59) 2020; 8
D Slade (43_CR65) 2011; 477
B Waszkowycz (43_CR73) 2018; 61
JM Pascal (43_CR52) 2015; 32
J Bhin (43_CR6) 2023; 42
W Li (43_CR42) 2014; 15
Evers (43_CR20) 2008; 14
A Ray Chaudhuri (43_CR58) 2017; 18
S Oka (43_CR50) 2006; 281
A Follenzi (43_CR24) 2000; 25
MP Dias (43_CR15) 2021; 18
K Tzelepis (43_CR69) 2016; 17
CT Rueden (43_CR60) 2017; 18
I-K Kim (43_CR36) 2012; 19
F Cortés-Ledesma (43_CR13) 2006; 7
K Jastrzebski (43_CR32) 2016; 1470
TA Ward (43_CR72) 2017; 12
G Keijzers (43_CR34) 2015; 35
D Szklarczyk (43_CR66) 2019; 47
JC Exell (43_CR21) 2016; 12
D Kim (43_CR35) 2022; 23
JE Ang (43_CR2) 2013; 19
A Ray Chaudhuri (43_CR57) 2015; 35
E Barkauskaite (43_CR4) 2013; 4
P Fontana (43_CR25) 2017; 6
AEO Fisher (43_CR23) 2007; 27
JS Baxter (43_CR5) 2022; 16
MM Murata (43_CR49) 2019; 30
D Ding (43_CR16) 2016; 2
B Lupo (43_CR45) 2014; 1846
D Lemaçon (43_CR40) 2017; 8
MI Love (43_CR44) 2014; 15
J Murai (43_CR47) 2012; 72
43_CR77
M Tallis (43_CR67) 2014; 123
MY Kim (43_CR37) 2005; 19
P ter Brugge (43_CR9) 2016; 108
KE Mengwasser (43_CR46) 2019; 73
W Sakai (43_CR61) 2008; 451
43_CR38
KK Lin (43_CR43) 2019; 9
AD D’Andrea (43_CR14) 2018; 71
EK Brinkman (43_CR7) 2014; 42
HE Bryant (43_CR10) 2005; 434
J Murai (43_CR48) 2014; 349
Y Pommier (43_CR55) 2016; 8
C-C Chen (43_CR11) 2018; 2
J O’Sullivan (43_CR51) 2019; 10
E Gogola (43_CR27) 2017; 3
SM Domchek (43_CR17) 2017; 7
J Jonkers (43_CR33) 2001; 29
References_xml – volume: 72
  start-page: 5588
  issue: 21
  year: 2012
  end-page: 5600
  ident: CR47
  article-title: Trapping of PARP1 and PARP2 by clinical PARP inhibitors
  publication-title: Cancer Res
– volume: 14
  start-page: 3916
  year: 2008
  end-page: 3925
  ident: CR20
  article-title: Selective inhibition of BRCA2-deficient mammary tumor cell growth by AZD2281 and cisplatin
  publication-title: Clin Cancer Res
– volume: 29
  start-page: 329
  year: 2022
  end-page: 338
  ident: CR71
  article-title: PARP inhibition impedes the maturation of nascent DNA strands during DNA replication
  publication-title: Nat Struct Mol Biol
– volume: 12
  start-page: e0179278
  year: 2017
  ident: CR72
  article-title: Small molecule inhibitors uncover synthetic genetic interactions of human flap endonuclease 1 (FEN1) with DNA damage response genes
  publication-title: PLoS ONE
– volume: 15
  year: 2014
  ident: CR44
  article-title: Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
  publication-title: Genome Biol
– volume: 25
  start-page: 217
  year: 2000
  end-page: 222
  ident: CR24
  article-title: Gene transfer by lentiviral vectors is limited by nuclear translocation and rescued by HIV-1 pol sequences
  publication-title: Nat Genet
– volume: 451
  start-page: 1111
  year: 2008
  end-page: 1115
  ident: CR19
  article-title: Resistance to therapy caused by intragenic deletion in BRCA2
  publication-title: Nature
– volume: 11
  year: 2020
  ident: CR29
  article-title: Pathogenic ARH3 mutations result in ADP-ribose chromatin scars during DNA strand break repair
  publication-title: Nat Commun
– volume: 35
  start-page: 519
  year: 2019
  end-page: 533.e8
  ident: CR54
  article-title: DNA replication vulnerabilities render ovarian cancer cells sensitive to Poly(ADP-Ribose) glycohydrolase inhibitors
  publication-title: Cancer Cell
– volume: 42
  start-page: e168
  issue: 22
  year: 2014
  ident: CR7
  article-title: Easy quantitative assessment of genome editing by sequence trace decomposition
  publication-title: Nucleic Acids Res
– volume: 2
  start-page: 16011
  year: 2016
  ident: CR16
  article-title: Induction and inhibition of the pan-nuclear gamma-H2AX response in resting human peripheral blood lymphocytes after X-ray irradiation
  publication-title: Cell death Discov
– ident: CR77
– volume: 34
  start-page: 360
  year: 2020
  end-page: 394
  ident: CR64
  article-title: PARP and PARG inhibitors in cancer treatment
  publication-title: Genes Dev
– volume: 42
  start-page: 112538
  year: 2023
  ident: CR6
  article-title: Multi-omics analysis reveals distinct non-reversion mechanisms of PARPi resistance in BRCA1- versus BRCA2-deficient mammary tumors
  publication-title: Cell Rep
– volume: 3
  start-page: 235
  issue: 1
  year: 2017
  end-page: 254
  ident: CR27
  article-title: Resistance to PARP inhibitors: lessons from preclinical models of BRCA-associated cancer
  publication-title: Annu Rev Cancer Bio
– volume: 205
  start-page: 613
  year: 2014
  end-page: 619
  ident: CR41
  article-title: Poly(ADP-ribose): an organizer of cellular architecture
  publication-title: J Cell Biol
– volume: 126
  start-page: 4414
  year: 2013
  end-page: 4423
  ident: CR74
  article-title: Damage response of XRCC1 at sites of DNA single strand breaks is regulated by phosphorylation and ubiquitylation after degradation of poly(ADP-ribose)
  publication-title: J Cell Sci
– volume: 434
  start-page: 917
  year: 2005
  ident: CR22
  article-title: Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
  publication-title: Nature
– volume: 9
  start-page: 210
  issue: 2
  year: 2019
  end-page: 219
  ident: CR43
  article-title: BRCA reversion mutations in circulating tumor DNA predict primary and acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma
  publication-title: Cancer Discov
– volume: 19
  start-page: 5485
  year: 2013
  end-page: 5493
  ident: CR2
  article-title: Efficacy of chemotherapy in BRCA1/2 mutation carrier ovarian cancer in the setting of PARP inhibitor resistance: a multi-institutional study
  publication-title: Clin Cancer Res
– volume: 7
  start-page: 919
  year: 2006
  end-page: 926
  ident: CR13
  article-title: Double-strand breaks arising by replication through a nick are repaired by cohesin-dependent sister-chromatid exchange
  publication-title: EMBO Rep
– volume: 32
  start-page: 1225
  year: 2013
  end-page: 1237
  ident: CR63
  article-title: Deficiency of terminal ADP-ribose protein glycohydrolase TARG1/C6orf130 in neurodegenerative disease
  publication-title: EMBO J
– volume: 98
  start-page: 8241
  year: 2001
  end-page: 8246
  ident: CR39
  article-title: Single-strand interruptions in replicating chromosomes cause double-strand breaks
  publication-title: Proc Natl Acad Sci USA
– volume: 349
  start-page: 408 LP
  year: 2014
  end-page: 416
  ident: CR48
  article-title: Rationale for Poly(ADP-ribose) polymerase (PARP) inhibitors in combination therapy with camptothecins or temozolomide based on PARP trapping versus catalytic inhibition
  publication-title: J Pharmacol Exp Ther
– volume: 3
  year: 2012
  ident: CR18
  article-title: Structure and mechanism of a canonical poly(ADP-ribose) glycohydrolase
  publication-title: Nat Commun
– volume: 32
  start-page: 10
  year: 2015
  end-page: 16
  ident: CR52
  article-title: The rise and fall of poly (ADP-ribose). An enzymatic perspective
  publication-title: DNA Repair
– volume: 434
  start-page: 913
  year: 2005
  end-page: 917
  ident: CR10
  article-title: Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase
  publication-title: Nature
– volume: 19
  start-page: 1951
  year: 2005
  end-page: 1967
  ident: CR37
  article-title: Poly(ADP-ribosyl)ation by PARP-1: ‘PAR-laying’ NAD+ into a nuclear signal
  publication-title: Genes Dev
– volume: 25
  start-page: 1147
  year: 2015
  end-page: 1157
  ident: CR76
  article-title: Sequence determinants of improved CRISPR sgRNA design
  publication-title: Genome Res
– volume: 229
  start-page: 422
  year: 2013
  end-page: 429
  ident: CR3
  article-title: Secondary mutations in BRCA2 associated with clinical resistance to a PARP inhibitor
  publication-title: J Pathol
– volume: 73
  start-page: 885
  year: 2019
  end-page: 899.e6
  ident: CR46
  article-title: Genetic screens reveal FEN1 and APEX2 as BRCA2 synthetic lethal targets
  publication-title: Mol Cell
– volume: 30
  start-page: 2584
  year: 2019
  end-page: 2597
  ident: CR49
  article-title: NAD+ consumption by PARP1 in response to DNA damage triggers metabolic shift critical for damaged cell survival
  publication-title: Mol Biol Cell
– volume: 2
  start-page: 313
  year: 2018
  end-page: 336
  ident: CR11
  article-title: Homology-directed repair and the role of BRCA1, BRCA2, and related proteins in genome integrity and cancer
  publication-title: Annu Rev Cancer Biol
– volume: 27
  start-page: 5597
  year: 2007
  end-page: 5605
  ident: CR23
  article-title: Poly(ADP-ribose) polymerase 1 accelerates single-strand break repair in concert with poly(ADP-ribose) glycohydrolase
  publication-title: Mol Cell Biol
– volume: 8
  start-page: 362ps17
  year: 2016
  ident: CR55
  article-title: Laying a trap to kill cancer cells: PARP inhibitors and their mechanisms of action
  publication-title: Sci Transl Med
– volume: 47
  start-page: 607
  year: 2019
  end-page: 613
  ident: CR66
  article-title: STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets
  publication-title: Nucleic Acids Res
– volume: 16
  start-page: 3811
  year: 2022
  end-page: 3827
  ident: CR5
  article-title: Resistance to DNA repair inhibitors in cancer
  publication-title: Mol Oncol
– volume: 5
  start-page: e10089
  year: 2010
  ident: CR70
  article-title: Emergence of micronuclei and their effects on the fate of cells under replication stress
  publication-title: PLoS ONE
– volume: 4
  year: 2013
  ident: CR4
  article-title: Visualization of poly(ADP-ribose) bound to PARG reveals inherent balance between exo- and endo-glycohydrolase activities
  publication-title: Nat Commun
– volume: 12
  start-page: 815
  year: 2016
  end-page: 821
  ident: CR21
  article-title: Cellularly active N-hydroxyurea FEN1 inhibitors block substrate entry to the active site
  publication-title: Nat Chem Biol
– volume: 451
  start-page: 1116
  year: 2008
  end-page: 1120
  ident: CR61
  article-title: Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers
  publication-title: Nature
– volume: 123
  start-page: 79
  year: 2014
  end-page: 90
  ident: CR67
  article-title: Poly(ADP-ribosyl)ation in regulation of chromatin structure and the DNA damage response
  publication-title: Chromosoma
– volume: 32
  start-page: 103
  year: 2021
  end-page: 112
  ident: CR68
  article-title: A meta-analysis of reversion mutations in BRCA genes identifies signatures of DNA end-joining repair mechanisms driving therapy resistance
  publication-title: Ann Oncol
– volume: 26
  start-page: 882
  year: 2004
  end-page: 893
  ident: CR1
  article-title: The PARP superfamily
  publication-title: Bioessays
– volume: 17
  start-page: 1193
  issue: 4
  year: 2016
  end-page: 1205
  ident: CR69
  article-title: A CRISPR dropout screen identifies genetic vulnerabilities and therapeutic targets in acute myeloid leukemia
  publication-title: Cell Rep
– volume: 10
  year: 2019
  ident: CR51
  article-title: Emerging roles of eraser enzymes in the dynamic control of protein ADP-ribosylation
  publication-title: Nat Commun
– volume: 18
  start-page: 610
  year: 2017
  ident: CR58
  article-title: The multifaceted roles of PARP1 in DNA repair and chromatin remodelling
  publication-title: Nat Rev Mol Cell Biol
– volume: 11
  start-page: 3179
  issue: 11
  year: 2016
  end-page: 3190
  ident: CR31
  article-title: First-in-class chemical probes against Poly(ADP-ribose) glycohydrolase (PARG) inhibit DNA repair with differential pharmacology to olaparib
  publication-title: ACS Chem Biol
– volume: 71
  start-page: 172
  year: 2018
  end-page: 176
  ident: CR14
  article-title: Mechanisms of PARP inhibitor sensitivity and resistance
  publication-title: DNA Repair
– volume: 8
  start-page: 564601
  year: 2020
  ident: CR59
  article-title: PARP inhibitors: clinical relevance, mechanisms of action and tumor resistance
  publication-title: Front cell Dev Biol
– volume: 15
  year: 2014
  ident: CR42
  article-title: MAGeCK enables robust identification of essential genes from genome-scale CRISPR/Cas9 knockout screens
  publication-title: Genome Biol
– volume: 108
  start-page: djw148
  year: 2016
  ident: CR9
  article-title: Mechanisms of therapy resistance in patient-derived xenograft models of BRCA1-deficient breast cancer
  publication-title: JNCI J Natl Cancer Inst
– volume: 6
  start-page: e18618
  year: 2011
  ident: CR75
  article-title: Replication stress induces micronuclei comprising of aggregated DNA double-strand breaks
  publication-title: PLoS ONE
– volume: 19
  start-page: 653
  year: 2012
  end-page: 656
  ident: CR36
  article-title: Structure of mammalian poly(ADP-ribose) glycohydrolase reveals a flexible tyrosine clasp as a substrate-binding element
  publication-title: Nat Struct Mol Biol
– volume: 33
  start-page: 1078
  year: 2018
  end-page: 1093.e12
  ident: CR26
  article-title: Selective loss of PARG restores PARylation and counteracts PARP inhibitor-mediated synthetic lethality
  publication-title: Cancer Cell
– volume: 1846
  start-page: 201
  year: 2014
  end-page: 215
  ident: CR45
  article-title: Inhibition of poly(ADP-ribosyl)ation in cancer: old and new paradigms revisited
  publication-title: Biochim Biophys Acta
– volume: 477
  start-page: 616
  year: 2011
  end-page: 620
  ident: CR65
  article-title: The structure and catalytic mechanism of a poly(ADP-ribose) glycohydrolase
  publication-title: Nature
– volume: 10
  year: 2019
  ident: CR30
  article-title: Selective small molecule PARG inhibitor causes replication fork stalling and cancer cell death
  publication-title: Nat Commun
– volume: 11
  start-page: 783
  year: 2014
  end-page: 784
  ident: CR62
  article-title: Improved vectors and genome-wide libraries for CRISPR screening
  publication-title: Nat Methods
– ident: CR38
– volume: 35
  start-page: e00206
  issue: 3
  year: 2015
  ident: CR34
  article-title: Human exonuclease 1 (EXO1) activity characterization and its function on flap structures
  publication-title: Biosci Rep
– volume: 163
  start-page: 160
  year: 2021
  end-page: 170
  ident: CR53
  article-title: DNA replication stress and emerging prospects for PARG inhibitors in ovarian cancer therapy
  publication-title: Prog Biophys Mol Biol
– volume: 61
  start-page: 10767
  issue: 23
  year: 2018
  end-page: 10792
  ident: CR73
  article-title: Cell-active small molecule inhibitors of the DNA-damage repair enzyme Poly(ADP-ribose) glycohydrolase (PARG): discovery and optimization of orally bioavailable quinazolinedione sulfonamides
  publication-title: J Med Chem
– volume: 71
  start-page: 319
  year: 2018
  end-page: 331.e3
  ident: CR28
  article-title: The importance of poly(ADP-Ribose) polymerase as a sensor of unligated Okazaki fragments during DNA replication
  publication-title: Mol Cell
– volume: 8
  year: 2017
  ident: CR40
  article-title: MRE11 and EXO1 nucleases degrade reversed forks and elicit MUS81-dependent fork rescue in BRCA2-deficient cells
  publication-title: Nat Commun
– volume: 7
  start-page: 937
  year: 2017
  end-page: 939
  ident: CR17
  article-title: Reversion mutations with clinical use of PARP inhibitors: many genes, many versions
  publication-title: Cancer Discov
– volume: 18
  start-page: 773
  year: 2021
  end-page: 791
  ident: CR15
  article-title: Understanding and overcoming resistance to PARP inhibitors in cancer therapy
  publication-title: Nat Rev Clin Oncol
– volume: 23
  start-page: 8412
  issue: 15
  year: 2022
  ident: CR35
  article-title: PARP inhibitors: clinical limitations and recent attempts to overcome them
  publication-title: Int J Mol Sci
– volume: 35
  start-page: 856
  year: 2015
  end-page: 865
  ident: CR57
  article-title: Poly(ADP-ribosyl) glycohydrolase prevents the accumulation of unusual replication structures during unperturbed S phase
  publication-title: Mol Cell Biol
– volume: 18
  year: 2017
  ident: CR60
  article-title: ImageJ2: ImageJ for the next generation of scientific image data
  publication-title: BMC Bioinforma
– volume: 6
  start-page: e28533
  year: 2017
  ident: CR25
  article-title: Serine ADP-ribosylation reversal by the hydrolase ARH3
  publication-title: eLife
– volume: 281
  start-page: 705
  year: 2006
  end-page: 713
  ident: CR50
  article-title: Identification and characterization of a mammalian 39-kDa poly(ADP-ribose) glycohydrolase
  publication-title: J Biol Chem
– volume: 5
  start-page: eaav4340
  issue: 4
  year: 2019
  ident: CR12
  article-title: Targeting dePARylation selectively suppresses DNA repair-defective and PARP inhibitor-resistant malignancies
  publication-title: Sci Adv
– volume: 70
  start-page: 801
  year: 2018
  end-page: 813.e6
  ident: CR8
  article-title: Kinetics and fidelity of the repair of Cas9-induced double-strand DNA breaks
  publication-title: Mol Cell
– volume: 1470
  start-page: 49
  year: 2016
  end-page: 73
  ident: CR32
  article-title: Pooled shRNA screening in mammalian cells as a functional genomic discovery platform
  publication-title: Methods Mol Biol
– volume: 591
  start-page: 55
  year: 2017
  end-page: 82
  ident: CR56
  article-title: DNA fiber analysis: mind the gap!
  publication-title: Methods Enzymol
– volume: 29
  start-page: 418
  year: 2001
  end-page: 425
  ident: CR33
  article-title: Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer
  publication-title: Nat Genet
– volume: 11
  start-page: 3179
  issue: 11
  year: 2016
  ident: 43_CR31
  publication-title: ACS Chem Biol
  doi: 10.1021/acschembio.6b00609
– volume: 11
  year: 2020
  ident: 43_CR29
  publication-title: Nat Commun
  doi: 10.1038/s41467-020-17069-9
– volume: 15
  year: 2014
  ident: 43_CR44
  publication-title: Genome Biol
– volume: 35
  start-page: 856
  year: 2015
  ident: 43_CR57
  publication-title: Mol Cell Biol
  doi: 10.1128/MCB.01077-14
– volume: 7
  start-page: 937
  year: 2017
  ident: 43_CR17
  publication-title: Cancer Discov
  doi: 10.1158/2159-8290.CD-17-0734
– volume: 27
  start-page: 5597
  year: 2007
  ident: 43_CR23
  publication-title: Mol Cell Biol
  doi: 10.1128/MCB.02248-06
– volume: 8
  year: 2017
  ident: 43_CR40
  publication-title: Nat Commun
  doi: 10.1038/s41467-017-01180-5
– volume: 26
  start-page: 882
  year: 2004
  ident: 43_CR1
  publication-title: Bioessays
  doi: 10.1002/bies.20085
– volume: 14
  start-page: 3916
  year: 2008
  ident: 43_CR20
  publication-title: Clin Cancer Res
  doi: 10.1158/1078-0432.CCR-07-4953
– volume: 18
  start-page: 610
  year: 2017
  ident: 43_CR58
  publication-title: Nat Rev Mol Cell Biol
  doi: 10.1038/nrm.2017.53
– volume: 434
  start-page: 917
  year: 2005
  ident: 43_CR22
  publication-title: Nature
  doi: 10.1038/nature03445
– volume: 6
  start-page: e28533
  year: 2017
  ident: 43_CR25
  publication-title: eLife
  doi: 10.7554/eLife.28533
– volume: 6
  start-page: e18618
  year: 2011
  ident: 43_CR75
  publication-title: PLoS ONE
  doi: 10.1371/journal.pone.0018618
– volume: 205
  start-page: 613
  year: 2014
  ident: 43_CR41
  publication-title: J Cell Biol
  doi: 10.1083/jcb.201402114
– volume: 32
  start-page: 103
  year: 2021
  ident: 43_CR68
  publication-title: Ann Oncol
  doi: 10.1016/j.annonc.2020.10.470
– volume: 12
  start-page: e0179278
  year: 2017
  ident: 43_CR72
  publication-title: PLoS ONE
  doi: 10.1371/journal.pone.0179278
– volume: 72
  start-page: 5588
  issue: 21
  year: 2012
  ident: 43_CR47
  publication-title: Cancer Res
  doi: 10.1158/0008-5472.CAN-12-2753
– volume: 5
  start-page: e10089
  year: 2010
  ident: 43_CR70
  publication-title: PLoS ONE
  doi: 10.1371/journal.pone.0010089
– ident: 43_CR38
  doi: 10.1016/j.molcel.2023.12.039
– volume: 34
  start-page: 360
  year: 2020
  ident: 43_CR64
  publication-title: Genes Dev
  doi: 10.1101/gad.334516.119
– volume: 11
  start-page: 783
  year: 2014
  ident: 43_CR62
  publication-title: Nat Methods
  doi: 10.1038/nmeth.3047
– volume: 3
  year: 2012
  ident: 43_CR18
  publication-title: Nat Commun
  doi: 10.1038/ncomms1889
– volume: 29
  start-page: 329
  year: 2022
  ident: 43_CR71
  publication-title: Nat Struct Mol Biol
  doi: 10.1038/s41594-022-00747-1
– volume: 8
  start-page: 564601
  year: 2020
  ident: 43_CR59
  publication-title: Front cell Dev Biol
  doi: 10.3389/fcell.2020.564601
– volume: 42
  start-page: e168
  issue: 22
  year: 2014
  ident: 43_CR7
  publication-title: Nucleic Acids Res
  doi: 10.1093/nar/gku936
– volume: 5
  start-page: eaav4340
  issue: 4
  year: 2019
  ident: 43_CR12
  publication-title: Sci Adv
  doi: 10.1126/sciadv.aav4340
– volume: 434
  start-page: 913
  year: 2005
  ident: 43_CR10
  publication-title: Nature
  doi: 10.1038/nature03443
– volume: 8
  start-page: 362ps17
  year: 2016
  ident: 43_CR55
  publication-title: Sci Transl Med
  doi: 10.1126/scitranslmed.aaf9246
– volume: 10
  year: 2019
  ident: 43_CR51
  publication-title: Nat Commun
  doi: 10.1038/s41467-019-08859-x
– volume: 61
  start-page: 10767
  issue: 23
  year: 2018
  ident: 43_CR73
  publication-title: J Med Chem
  doi: 10.1021/acs.jmedchem.8b01407
– volume: 25
  start-page: 1147
  year: 2015
  ident: 43_CR76
  publication-title: Genome Res
  doi: 10.1101/gr.191452.115
– volume: 23
  start-page: 8412
  issue: 15
  year: 2022
  ident: 43_CR35
  publication-title: Int J Mol Sci
  doi: 10.3390/ijms23158412
– volume: 19
  start-page: 653
  year: 2012
  ident: 43_CR36
  publication-title: Nat Struct Mol Biol
  doi: 10.1038/nsmb.2305
– volume: 32
  start-page: 1225
  year: 2013
  ident: 43_CR63
  publication-title: EMBO J
  doi: 10.1038/emboj.2013.51
– volume: 30
  start-page: 2584
  year: 2019
  ident: 43_CR49
  publication-title: Mol Biol Cell
  doi: 10.1091/mbc.E18-10-0650
– volume: 18
  year: 2017
  ident: 43_CR60
  publication-title: BMC Bioinforma
  doi: 10.1186/s12859-017-1934-z
– volume: 451
  start-page: 1111
  year: 2008
  ident: 43_CR19
  publication-title: Nature
  doi: 10.1038/nature06548
– volume: 3
  start-page: 235
  issue: 1
  year: 2017
  ident: 43_CR27
  publication-title: Annu Rev Cancer Bio
  doi: 10.1146/annurev-cancerbio-030617-050232
– volume: 18
  start-page: 773
  year: 2021
  ident: 43_CR15
  publication-title: Nat Rev Clin Oncol
  doi: 10.1038/s41571-021-00532-x
– volume: 12
  start-page: 815
  year: 2016
  ident: 43_CR21
  publication-title: Nat Chem Biol
  doi: 10.1038/nchembio.2148
– volume: 19
  start-page: 1951
  year: 2005
  ident: 43_CR37
  publication-title: Genes Dev
  doi: 10.1101/gad.1331805
– volume: 108
  start-page: djw148
  year: 2016
  ident: 43_CR9
  publication-title: JNCI J Natl Cancer Inst
  doi: 10.1093/jnci/djw148
– volume: 4
  year: 2013
  ident: 43_CR4
  publication-title: Nat Commun
  doi: 10.1038/ncomms3164
– volume: 126
  start-page: 4414
  year: 2013
  ident: 43_CR74
  publication-title: J Cell Sci
  doi: 10.1242/jcs.128272
– volume: 98
  start-page: 8241
  year: 2001
  ident: 43_CR39
  publication-title: Proc Natl Acad Sci USA
  doi: 10.1073/pnas.131009198
– volume: 15
  year: 2014
  ident: 43_CR42
  publication-title: Genome Biol
– volume: 281
  start-page: 705
  year: 2006
  ident: 43_CR50
  publication-title: J Biol Chem
  doi: 10.1074/jbc.M510290200
– volume: 163
  start-page: 160
  year: 2021
  ident: 43_CR53
  publication-title: Prog Biophys Mol Biol
  doi: 10.1016/j.pbiomolbio.2021.01.004
– volume: 19
  start-page: 5485
  year: 2013
  ident: 43_CR2
  publication-title: Clin Cancer Res
  doi: 10.1158/1078-0432.CCR-13-1262
– volume: 10
  year: 2019
  ident: 43_CR30
  publication-title: Nat Commun
– volume: 591
  start-page: 55
  year: 2017
  ident: 43_CR56
  publication-title: Methods Enzymol
  doi: 10.1016/bs.mie.2017.03.019
– volume: 2
  start-page: 313
  year: 2018
  ident: 43_CR11
  publication-title: Annu Rev Cancer Biol
  doi: 10.1146/annurev-cancerbio-030617-050502
– volume: 229
  start-page: 422
  year: 2013
  ident: 43_CR3
  publication-title: J Pathol
  doi: 10.1002/path.4140
– volume: 349
  start-page: 408 LP
  year: 2014
  ident: 43_CR48
  publication-title: J Pharmacol Exp Ther
  doi: 10.1124/jpet.113.210146
– volume: 33
  start-page: 1078
  year: 2018
  ident: 43_CR26
  publication-title: Cancer Cell
  doi: 10.1016/j.ccell.2018.05.008
– volume: 477
  start-page: 616
  year: 2011
  ident: 43_CR65
  publication-title: Nature
  doi: 10.1038/nature10404
– volume: 29
  start-page: 418
  year: 2001
  ident: 43_CR33
  publication-title: Nat Genet
  doi: 10.1038/ng747
– volume: 1846
  start-page: 201
  year: 2014
  ident: 43_CR45
  publication-title: Biochim Biophys Acta
– volume: 70
  start-page: 801
  year: 2018
  ident: 43_CR8
  publication-title: Mol Cell
  doi: 10.1016/j.molcel.2018.04.016
– volume: 17
  start-page: 1193
  issue: 4
  year: 2016
  ident: 43_CR69
  publication-title: Cell Rep
  doi: 10.1016/j.celrep.2016.09.079
– volume: 71
  start-page: 172
  year: 2018
  ident: 43_CR14
  publication-title: DNA Repair
  doi: 10.1016/j.dnarep.2018.08.021
– volume: 25
  start-page: 217
  year: 2000
  ident: 43_CR24
  publication-title: Nat Genet
  doi: 10.1038/76095
– volume: 32
  start-page: 10
  year: 2015
  ident: 43_CR52
  publication-title: DNA Repair
  doi: 10.1016/j.dnarep.2015.04.008
– ident: 43_CR77
  doi: 10.1016/S0076-6879(05)09024-5
– volume: 7
  start-page: 919
  year: 2006
  ident: 43_CR13
  publication-title: EMBO Rep
  doi: 10.1038/sj.embor.7400774
– volume: 42
  start-page: 112538
  year: 2023
  ident: 43_CR6
  publication-title: Cell Rep
  doi: 10.1016/j.celrep.2023.112538
– volume: 1470
  start-page: 49
  year: 2016
  ident: 43_CR32
  publication-title: Methods Mol Biol
  doi: 10.1007/978-1-4939-6337-9_5
– volume: 35
  start-page: e00206
  issue: 3
  year: 2015
  ident: 43_CR34
  publication-title: Biosci Rep
  doi: 10.1042/BSR20150058
– volume: 16
  start-page: 3811
  year: 2022
  ident: 43_CR5
  publication-title: Mol Oncol
  doi: 10.1002/1878-0261.13224
– volume: 451
  start-page: 1116
  year: 2008
  ident: 43_CR61
  publication-title: Nature
  doi: 10.1038/nature06633
– volume: 71
  start-page: 319
  year: 2018
  ident: 43_CR28
  publication-title: Mol Cell
  doi: 10.1016/j.molcel.2018.06.004
– volume: 73
  start-page: 885
  year: 2019
  ident: 43_CR46
  publication-title: Mol Cell
  doi: 10.1016/j.molcel.2018.12.008
– volume: 35
  start-page: 519
  year: 2019
  ident: 43_CR54
  publication-title: Cancer Cell
  doi: 10.1016/j.ccell.2019.02.004
– volume: 47
  start-page: 607
  year: 2019
  ident: 43_CR66
  publication-title: Nucleic Acids Res
  doi: 10.1093/nar/gky1131
– volume: 123
  start-page: 79
  year: 2014
  ident: 43_CR67
  publication-title: Chromosoma
  doi: 10.1007/s00412-013-0442-9
– volume: 2
  start-page: 16011
  year: 2016
  ident: 43_CR16
  publication-title: Cell death Discov
  doi: 10.1038/cddiscovery.2016.11
– volume: 9
  start-page: 210
  issue: 2
  year: 2019
  ident: 43_CR43
  publication-title: Cancer Discov
  doi: 10.1158/2159-8290.CD-18-0715
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Snippet Targeting poly(ADP-ribose) glycohydrolase (PARG) is currently explored as a therapeutic approach to treat various cancer types, but we have a poor...
SourceID pubmedcentral
proquest
pubmed
crossref
springer
SourceType Open Access Repository
Aggregation Database
Index Database
Enrichment Source
Publisher
StartPage 1015
SubjectTerms Biomedical and Life Sciences
DNA Damage
DNA Repair
DNA Repair Enzymes - genetics
EMBO03
EMBO13
EMBO31
Exodeoxyribonucleases - genetics
Flap Endonucleases - genetics
Flap Endonucleases - metabolism
Flap Endonucleases - therapeutic use
Glycoside Hydrolases - genetics
Glycoside Hydrolases - metabolism
Humans
Life Sciences
Neoplasms - drug therapy
Neoplasms - genetics
Poly(ADP-ribose) Polymerase Inhibitors - pharmacology
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
Title PARG-deficient tumor cells have an increased dependence on EXO1/FEN1-mediated DNA repair
URI https://link.springer.com/article/10.1038/s44318-024-00043-2
https://www.ncbi.nlm.nih.gov/pubmed/38360994
https://www.proquest.com/docview/2928247262
https://pubmed.ncbi.nlm.nih.gov/PMC10943112
Volume 43
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