ATR prohibits replication catastrophe by preventing global exhaustion of RPA
ATR, activated by replication stress, protects replication forks locally and suppresses origin firing globally. Here, we show that these functions of ATR are mechanistically coupled. Although initially stable, stalled forks in ATR-deficient cells undergo nucleus-wide breakage after unscheduled origi...
Saved in:
| Published in: | Cell Vol. 155; no. 5; p. 1088 |
|---|---|
| Main Authors: | , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
21.11.2013
|
| Subjects: | |
| ISSN: | 1097-4172, 1097-4172 |
| Online Access: | Get more information |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Abstract | ATR, activated by replication stress, protects replication forks locally and suppresses origin firing globally. Here, we show that these functions of ATR are mechanistically coupled. Although initially stable, stalled forks in ATR-deficient cells undergo nucleus-wide breakage after unscheduled origin firing generates an excess of single-stranded DNA that exhausts the nuclear pool of RPA. Partial reduction of RPA accelerated fork breakage, and forced elevation of RPA was sufficient to delay such "replication catastrophe" even in the absence of ATR activity. Conversely, unscheduled origin firing induced breakage of stalled forks even in cells with active ATR. Thus, ATR-mediated suppression of dormant origins shields active forks against irreversible breakage via preventing exhaustion of nuclear RPA. This study elucidates how replicating genomes avoid destabilizing DNA damage. Because cancer cells commonly feature intrinsically high replication stress, this study also provides a molecular rationale for their hypersensitivity to ATR inhibitors. |
|---|---|
| AbstractList | ATR, activated by replication stress, protects replication forks locally and suppresses origin firing globally. Here, we show that these functions of ATR are mechanistically coupled. Although initially stable, stalled forks in ATR-deficient cells undergo nucleus-wide breakage after unscheduled origin firing generates an excess of single-stranded DNA that exhausts the nuclear pool of RPA. Partial reduction of RPA accelerated fork breakage, and forced elevation of RPA was sufficient to delay such "replication catastrophe" even in the absence of ATR activity. Conversely, unscheduled origin firing induced breakage of stalled forks even in cells with active ATR. Thus, ATR-mediated suppression of dormant origins shields active forks against irreversible breakage via preventing exhaustion of nuclear RPA. This study elucidates how replicating genomes avoid destabilizing DNA damage. Because cancer cells commonly feature intrinsically high replication stress, this study also provides a molecular rationale for their hypersensitivity to ATR inhibitors.ATR, activated by replication stress, protects replication forks locally and suppresses origin firing globally. Here, we show that these functions of ATR are mechanistically coupled. Although initially stable, stalled forks in ATR-deficient cells undergo nucleus-wide breakage after unscheduled origin firing generates an excess of single-stranded DNA that exhausts the nuclear pool of RPA. Partial reduction of RPA accelerated fork breakage, and forced elevation of RPA was sufficient to delay such "replication catastrophe" even in the absence of ATR activity. Conversely, unscheduled origin firing induced breakage of stalled forks even in cells with active ATR. Thus, ATR-mediated suppression of dormant origins shields active forks against irreversible breakage via preventing exhaustion of nuclear RPA. This study elucidates how replicating genomes avoid destabilizing DNA damage. Because cancer cells commonly feature intrinsically high replication stress, this study also provides a molecular rationale for their hypersensitivity to ATR inhibitors. ATR, activated by replication stress, protects replication forks locally and suppresses origin firing globally. Here, we show that these functions of ATR are mechanistically coupled. Although initially stable, stalled forks in ATR-deficient cells undergo nucleus-wide breakage after unscheduled origin firing generates an excess of single-stranded DNA that exhausts the nuclear pool of RPA. Partial reduction of RPA accelerated fork breakage, and forced elevation of RPA was sufficient to delay such "replication catastrophe" even in the absence of ATR activity. Conversely, unscheduled origin firing induced breakage of stalled forks even in cells with active ATR. Thus, ATR-mediated suppression of dormant origins shields active forks against irreversible breakage via preventing exhaustion of nuclear RPA. This study elucidates how replicating genomes avoid destabilizing DNA damage. Because cancer cells commonly feature intrinsically high replication stress, this study also provides a molecular rationale for their hypersensitivity to ATR inhibitors. |
| Author | Rask, Maj-Britt Povlsen, Lou Klitgaard Mailand, Niels Lukas, Jiri Lukas, Claudia Bartek, Jiri Toledo, Luis Ignacio Larsen, Dorthe Helena Altmeyer, Matthias Bekker-Jensen, Simon |
| Author_xml | – sequence: 1 givenname: Luis Ignacio surname: Toledo fullname: Toledo, Luis Ignacio organization: Chromosome Stability and Dynamics Group, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark – sequence: 2 givenname: Matthias surname: Altmeyer fullname: Altmeyer, Matthias – sequence: 3 givenname: Maj-Britt surname: Rask fullname: Rask, Maj-Britt – sequence: 4 givenname: Claudia surname: Lukas fullname: Lukas, Claudia – sequence: 5 givenname: Dorthe Helena surname: Larsen fullname: Larsen, Dorthe Helena – sequence: 6 givenname: Lou Klitgaard surname: Povlsen fullname: Povlsen, Lou Klitgaard – sequence: 7 givenname: Simon surname: Bekker-Jensen fullname: Bekker-Jensen, Simon – sequence: 8 givenname: Niels surname: Mailand fullname: Mailand, Niels – sequence: 9 givenname: Jiri surname: Bartek fullname: Bartek, Jiri – sequence: 10 givenname: Jiri surname: Lukas fullname: Lukas, Jiri |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/24267891$$D View this record in MEDLINE/PubMed |
| BookMark | eNpNkEtLw0AcxBep2Id-AQ-yRy-J-8o-jqX4goJS6jlskn-aLWk2ZhOx396oFTzNMPwYhpmjSeMbQOiakpgSKu_2cQ51HTNC-RjERPAzNKPEqEhQxSb__BTNQ9gTQnSSJBdoygSTShs6Q-vldoPbzlcuc33AHbS1y23vfINHsaHvfFsBzo4jBB_Q9K7Z4V3tM1tj-KzsEH5YX-LN6_ISnZe2DnB10gV6e7jfrp6i9cvj82q5jnKR8D7KC5EbAZoXjACjBQXDDJRGmzLhhaaCJVYapSQZXUaBa6ZUpiUBJZmGgi3Q7W_vOPx9gNCnBxe-v7AN-CGkVEiqpRFcjujNCR2yAxRp27mD7Y7p3wPsC-7aX4A |
| CitedBy_id | crossref_primary_10_3390_genes5010147 crossref_primary_10_1038_s41467_023_40779_9 crossref_primary_10_1158_0008_5472_CAN_16_3389 crossref_primary_10_1158_1541_7786_MCR_18_0860 crossref_primary_10_1186_s13578_021_00616_2 crossref_primary_10_1038_s41416_020_1016_2 crossref_primary_10_1002_2211_5463_12632 crossref_primary_10_1038_s41467_022_33887_5 crossref_primary_10_1038_s41467_024_52862_w crossref_primary_10_15252_embj_2019101801 crossref_primary_10_1016_j_molcel_2021_09_005 crossref_primary_10_1016_j_molcel_2018_11_036 crossref_primary_10_1038_s41586_020_2769_8 crossref_primary_10_1038_s41586_018_0261_5 crossref_primary_10_1093_nar_gkt1412 crossref_primary_10_3390_biomedicines12040762 crossref_primary_10_3390_ijms23031116 crossref_primary_10_1016_j_mrfmmm_2020_111725 crossref_primary_10_1158_2159_8290_CD_17_1461 crossref_primary_10_1080_15384101_2017_1383578 crossref_primary_10_1182_blood_2021014103 crossref_primary_10_1093_nar_gkab628 crossref_primary_10_1074_jbc_M115_685883 crossref_primary_10_15252_embj_2018101379 crossref_primary_10_1172_JCI96769 crossref_primary_10_1038_s41594_024_01417_0 crossref_primary_10_1016_j_semcdb_2014_04_035 crossref_primary_10_1038_s41467_024_45946_0 crossref_primary_10_1007_s00412_016_0573_x crossref_primary_10_1002_cncr_32004 crossref_primary_10_3390_cancers13133346 crossref_primary_10_1016_j_bpc_2016_11_005 crossref_primary_10_1016_j_molcel_2020_08_018 crossref_primary_10_3389_fonc_2023_1210487 crossref_primary_10_1038_s41556_023_01280_z crossref_primary_10_1126_sciadv_aay4697 crossref_primary_10_26508_lsa_202101023 crossref_primary_10_1111_cas_15477 crossref_primary_10_1016_j_neo_2024_101038 crossref_primary_10_1016_j_celrep_2024_115114 crossref_primary_10_1371_journal_pgen_1005517 crossref_primary_10_1016_j_canlet_2016_09_024 crossref_primary_10_1242_jcs_169730 crossref_primary_10_1158_1078_0432_CCR_16_1782 crossref_primary_10_1126_science_aao3172 crossref_primary_10_3390_cancers11091320 crossref_primary_10_1038_s41586_020_2842_3 crossref_primary_10_3390_cells9071657 crossref_primary_10_1093_g3journal_jkac116 crossref_primary_10_1007_s00018_019_03208_z crossref_primary_10_1007_s12268_018_0918_5 crossref_primary_10_1371_journal_pbio_3001543 crossref_primary_10_1016_j_tibs_2019_03_011 crossref_primary_10_1073_pnas_2020185118 crossref_primary_10_1016_j_molcel_2019_05_015 crossref_primary_10_1007_s00294_018_0873_1 crossref_primary_10_1073_pnas_2413732122 crossref_primary_10_26508_lsa_201900547 crossref_primary_10_1038_s42003_024_05855_w crossref_primary_10_1007_s00294_019_00945_3 crossref_primary_10_1038_ncomms14432 crossref_primary_10_1038_s41467_017_00221_3 crossref_primary_10_1016_j_semcancer_2021_04_012 crossref_primary_10_1002_bies_201400161 crossref_primary_10_1038_ncb3367 crossref_primary_10_1038_s41598_022_08850_5 crossref_primary_10_1016_j_coi_2018_09_017 crossref_primary_10_1016_j_freeradbiomed_2025_06_008 crossref_primary_10_1016_j_jmb_2014_08_022 crossref_primary_10_1038_s41419_020_03231_0 crossref_primary_10_1038_s41467_025_58183_w crossref_primary_10_1002_1878_0261_12882 crossref_primary_10_1073_pnas_2106393118 crossref_primary_10_1016_j_molcel_2021_01_004 crossref_primary_10_1016_j_semcancer_2016_01_001 crossref_primary_10_1158_1078_0432_CCR_22_2587 crossref_primary_10_1038_s41388_020_1191_x crossref_primary_10_1038_s44319_024_00085_x crossref_primary_10_1093_nar_gkad839 crossref_primary_10_1038_nprot_2015_066 crossref_primary_10_1242_jcs_261844 crossref_primary_10_1016_j_semcdb_2018_04_005 crossref_primary_10_1002_ijc_32966 crossref_primary_10_1016_j_cancergen_2025_09_002 crossref_primary_10_1016_j_molcel_2018_02_024 crossref_primary_10_1016_j_molcel_2018_02_023 crossref_primary_10_1093_nar_gkae811 crossref_primary_10_1038_cr_2015_115 crossref_primary_10_1038_s41467_022_30215_9 crossref_primary_10_1158_1541_7786_MCR_18_0551 crossref_primary_10_3390_biom5031912 crossref_primary_10_1016_j_eururo_2020_10_029 crossref_primary_10_1002_bies_202200061 crossref_primary_10_1093_nar_gkab551 crossref_primary_10_1007_s00018_019_03206_1 crossref_primary_10_1016_j_molcel_2017_09_018 crossref_primary_10_1093_neuonc_noz159 crossref_primary_10_1016_j_dnarep_2021_103163 crossref_primary_10_1002_pmic_201500172 crossref_primary_10_3389_fimmu_2022_765284 crossref_primary_10_1038_s44318_024_00066_9 crossref_primary_10_1158_0008_5472_CAN_18_1877 crossref_primary_10_3389_fmolb_2021_712971 crossref_primary_10_1038_s41418_023_01196_z crossref_primary_10_1016_j_devcel_2021_01_011 crossref_primary_10_1016_j_cub_2015_09_026 crossref_primary_10_1074_jbc_C116_747758 crossref_primary_10_1186_s13073_021_00981_0 crossref_primary_10_15252_embr_201948920 crossref_primary_10_1016_j_jbc_2021_101301 crossref_primary_10_1186_s13058_022_01586_0 crossref_primary_10_1042_BST20190363 crossref_primary_10_15252_embj_2018101284 crossref_primary_10_1093_nar_gkad940 crossref_primary_10_1016_j_exphem_2022_03_008 crossref_primary_10_3389_fcell_2021_702584 crossref_primary_10_3389_fonc_2022_826655 crossref_primary_10_1016_j_canlet_2022_215804 crossref_primary_10_1038_s41467_021_23806_5 crossref_primary_10_1038_s41586_019_1659_4 crossref_primary_10_1182_blood_2015_05_644872 crossref_primary_10_1016_j_dnarep_2015_04_026 crossref_primary_10_1016_j_tibs_2020_05_003 crossref_primary_10_1074_jbc_M116_772475 crossref_primary_10_1016_j_dnarep_2023_103611 crossref_primary_10_1038_s41467_025_59804_0 crossref_primary_10_1371_journal_pbio_3002552 crossref_primary_10_1016_j_molcel_2023_06_025 crossref_primary_10_1016_j_freeradbiomed_2016_11_039 crossref_primary_10_1038_srep19567 crossref_primary_10_3389_fonc_2022_838637 crossref_primary_10_1093_nar_gkac741 crossref_primary_10_1158_2159_8290_CD_16_0612 crossref_primary_10_15252_embj_201796631 crossref_primary_10_1016_j_dnarep_2018_09_010 crossref_primary_10_3390_genes13050803 crossref_primary_10_34133_research_0862 crossref_primary_10_1158_0008_5472_CAN_20_2860 crossref_primary_10_1038_s41591_023_02399_0 crossref_primary_10_1038_s41388_019_0814_6 crossref_primary_10_1016_j_molonc_2014_09_012 crossref_primary_10_1111_cas_15845 crossref_primary_10_1074_jbc_M115_644005 crossref_primary_10_1126_sciadv_adu0437 crossref_primary_10_3390_ijms18061233 crossref_primary_10_1038_s41467_020_17324_z crossref_primary_10_1083_jcb_201506071 crossref_primary_10_1080_15384101_2016_1184512 crossref_primary_10_1126_science_aap9346 crossref_primary_10_15252_embj_2021108813 crossref_primary_10_3390_cancers12102809 crossref_primary_10_1038_ncomms13398 crossref_primary_10_1016_j_mrfmmm_2023_111834 crossref_primary_10_1016_j_lfs_2023_122131 crossref_primary_10_1016_j_dnarep_2014_03_012 crossref_primary_10_1038_s41467_017_00634_0 crossref_primary_10_1002_bies_201400107 crossref_primary_10_3390_ijms19082376 crossref_primary_10_3390_ijms241612978 crossref_primary_10_15252_embj_201591293 crossref_primary_10_1016_j_molcel_2017_06_023 crossref_primary_10_1073_pnas_1917196117 crossref_primary_10_1007_s00280_019_03950_y crossref_primary_10_1101_gad_334516_119 crossref_primary_10_1038_s41467_023_38417_5 crossref_primary_10_1016_j_dnarep_2022_103418 crossref_primary_10_1016_j_molcel_2015_06_026 crossref_primary_10_1038_s41598_021_92631_z crossref_primary_10_3390_genes11060642 crossref_primary_10_1007_s00204_018_2202_3 crossref_primary_10_1016_j_radonc_2017_09_043 crossref_primary_10_1038_s41586_018_0534_z crossref_primary_10_1002_1878_0261_13819 crossref_primary_10_3390_genes8030092 crossref_primary_10_1016_j_cub_2014_04_012 crossref_primary_10_1016_j_jtho_2019_01_028 crossref_primary_10_1016_j_molcel_2022_05_004 crossref_primary_10_3390_genes12040552 crossref_primary_10_1371_journal_ppat_1008403 crossref_primary_10_3390_ijms231911331 crossref_primary_10_15252_embj_2020106336 crossref_primary_10_1038_s41388_019_1079_9 crossref_primary_10_1038_s41467_023_38711_2 crossref_primary_10_1073_pnas_1904024116 crossref_primary_10_1038_s41467_024_55637_5 crossref_primary_10_1101_gad_352311_124 crossref_primary_10_1158_0008_5472_CAN_17_3932 crossref_primary_10_3390_cancers13184681 crossref_primary_10_1016_j_ebiom_2017_09_016 crossref_primary_10_3390_genes8020049 crossref_primary_10_1083_jcb_201902085 crossref_primary_10_3390_ijms21249431 crossref_primary_10_1002_path_4828 crossref_primary_10_1016_j_molcel_2023_07_026 crossref_primary_10_1146_annurev_genet_120116_024745 crossref_primary_10_3390_cancers11091289 crossref_primary_10_1080_15384101_2017_1288322 crossref_primary_10_1038_s41586_024_07112_w crossref_primary_10_1016_j_isci_2021_102313 crossref_primary_10_1038_s41467_025_60160_2 crossref_primary_10_3389_fcell_2021_714868 crossref_primary_10_1016_j_molcel_2018_01_012 crossref_primary_10_1038_cr_2014_147 crossref_primary_10_1038_s41467_023_36149_0 crossref_primary_10_1098_rsob_190156 crossref_primary_10_1038_s41598_017_09716_x crossref_primary_10_3389_fgene_2015_00070 crossref_primary_10_3390_biom10030463 crossref_primary_10_1038_s41467_019_12064_1 crossref_primary_10_1080_15384101_2014_997517 crossref_primary_10_1073_pnas_2019183118 crossref_primary_10_3390_diagnostics10020121 crossref_primary_10_1016_j_molcel_2016_05_007 crossref_primary_10_1093_nar_gkac1121 crossref_primary_10_1158_0008_5472_CAN_18_3631 crossref_primary_10_15252_embr_202357677 crossref_primary_10_1016_j_dnarep_2021_103209 crossref_primary_10_1016_j_cell_2018_03_050 crossref_primary_10_1016_j_aquaculture_2024_741146 crossref_primary_10_26508_lsa_202201560 crossref_primary_10_1158_1078_0432_CCR_19_0448 crossref_primary_10_1016_j_semcancer_2018_08_003 crossref_primary_10_1038_ncb3415 crossref_primary_10_1038_s41556_020_0494_z crossref_primary_10_1038_s41467_021_25827_6 crossref_primary_10_3389_fcimb_2021_802613 crossref_primary_10_1073_pnas_2017497118 crossref_primary_10_1146_annurev_genet_120213_092228 crossref_primary_10_3389_fcell_2020_00416 crossref_primary_10_3390_cells12141904 crossref_primary_10_1038_s41388_020_1220_9 crossref_primary_10_1038_s41594_023_00932_w crossref_primary_10_1016_j_tranon_2018_06_008 crossref_primary_10_1038_s41467_019_10180_6 crossref_primary_10_1038_s41467_023_37341_y crossref_primary_10_1038_s41388_021_02080_1 crossref_primary_10_1016_j_bbagrm_2014_04_008 crossref_primary_10_3390_cancers14235722 crossref_primary_10_1371_journal_pone_0091222 crossref_primary_10_1038_ncb3422 crossref_primary_10_1038_s41467_024_52189_6 crossref_primary_10_1093_nar_gkad659 crossref_primary_10_1093_nar_gku505 crossref_primary_10_1093_nar_gkv957 crossref_primary_10_1038_ncomms9088 crossref_primary_10_1038_s41467_025_60077_w crossref_primary_10_1002_hem3_70016 crossref_primary_10_1093_nar_gkv835 crossref_primary_10_3390_cells9071747 crossref_primary_10_1038_s41467_023_39332_5 crossref_primary_10_12677_WJCR_2022_122006 crossref_primary_10_1016_j_crmeth_2023_100501 crossref_primary_10_1038_s41588_023_01458_z crossref_primary_10_1016_j_molcel_2021_04_006 crossref_primary_10_1016_j_molcel_2022_12_004 crossref_primary_10_1074_jbc_RA118_005231 crossref_primary_10_1093_nar_gkae1159 crossref_primary_10_1146_annurev_genet_121415_121658 crossref_primary_10_1158_0008_5472_CAN_17_2802 crossref_primary_10_1007_s10585_024_10265_7 crossref_primary_10_1038_s41467_024_46358_w crossref_primary_10_3390_ijms18071339 crossref_primary_10_1016_j_cell_2014_05_046 crossref_primary_10_1038_ncb3436 crossref_primary_10_1038_s41586_022_04638_9 crossref_primary_10_1016_j_celrep_2023_113412 crossref_primary_10_1038_s41388_020_1265_9 crossref_primary_10_15252_embr_202357585 crossref_primary_10_1016_j_molcel_2018_09_014 crossref_primary_10_1093_nar_gkw1125 crossref_primary_10_1016_j_devcel_2016_11_017 crossref_primary_10_1093_nar_gkac214 crossref_primary_10_3390_genes8020074 crossref_primary_10_1111_febs_12867 crossref_primary_10_1186_s13048_023_01094_5 crossref_primary_10_3390_biology11111652 crossref_primary_10_3390_genes8010037 crossref_primary_10_1016_j_neo_2018_08_001 crossref_primary_10_1016_j_cell_2016_09_054 crossref_primary_10_1073_pnas_1720355115 crossref_primary_10_3389_fonc_2022_828684 crossref_primary_10_1016_j_lfs_2023_122085 crossref_primary_10_1093_nar_gkab134 crossref_primary_10_1073_pnas_2013921117 crossref_primary_10_1016_j_jbc_2023_104900 crossref_primary_10_1038_s41598_018_21110_9 crossref_primary_10_1038_s41586_021_03526_y crossref_primary_10_1172_JCI165448 crossref_primary_10_1186_s12964_024_01513_0 crossref_primary_10_1093_nar_gky1242 crossref_primary_10_1016_j_cub_2014_03_060 crossref_primary_10_1093_nar_gkz1167 crossref_primary_10_7554_eLife_57894 crossref_primary_10_1016_j_cell_2013_10_049 crossref_primary_10_1080_15384101_2019_1593649 crossref_primary_10_1016_j_dnarep_2025_103887 crossref_primary_10_15252_embr_202050662 crossref_primary_10_1073_pnas_1400683111 crossref_primary_10_1177_1758835918786658 crossref_primary_10_1016_j_molcel_2019_08_023 crossref_primary_10_1093_carcin_bgaa021 crossref_primary_10_3390_ijms21051588 crossref_primary_10_1242_jcs_161596 crossref_primary_10_1093_nar_gkaf544 crossref_primary_10_1093_nar_gkad363 crossref_primary_10_3390_genes9120603 crossref_primary_10_1038_s41594_023_00998_6 crossref_primary_10_1038_s41467_025_63002_3 crossref_primary_10_1016_j_isci_2025_112567 crossref_primary_10_1093_nar_gkad369 crossref_primary_10_1016_j_dnarep_2017_03_006 crossref_primary_10_1038_s41467_024_48286_1 crossref_primary_10_1038_s41598_021_00435_y crossref_primary_10_1038_s41420_024_02083_3 crossref_primary_10_3389_fcell_2020_602956 crossref_primary_10_1016_j_bbamcr_2023_119484 crossref_primary_10_1158_1078_0432_CCR_17_2701 crossref_primary_10_1083_jcb_201809012 crossref_primary_10_1093_g3journal_jkae196 crossref_primary_10_1038_s41388_022_02291_0 crossref_primary_10_1016_j_molcel_2020_04_031 crossref_primary_10_1146_annurev_pathol_012414_040424 crossref_primary_10_1111_febs_13898 crossref_primary_10_1038_s41467_021_26049_6 crossref_primary_10_1038_s41467_024_46760_4 crossref_primary_10_1016_j_pt_2017_08_002 crossref_primary_10_1038_s44319_025_00514_5 crossref_primary_10_1038_s41388_017_0121_z crossref_primary_10_1172_JCI189511 crossref_primary_10_1016_j_molcel_2022_07_011 crossref_primary_10_1080_15384101_2016_1148841 crossref_primary_10_1080_10409238_2018_1488803 crossref_primary_10_1038_s41467_022_32861_5 crossref_primary_10_1093_nar_gkae546 crossref_primary_10_1016_j_celrep_2025_116090 crossref_primary_10_1016_j_dnarep_2025_103865 crossref_primary_10_1038_s41467_021_27057_2 crossref_primary_10_15252_embr_201744877 crossref_primary_10_1038_s41467_018_08048_2 crossref_primary_10_1016_j_canlet_2025_218009 crossref_primary_10_1016_j_molonc_2014_11_001 crossref_primary_10_1038_nsmb_3163 crossref_primary_10_1038_s41598_018_32323_3 crossref_primary_10_1016_j_molcel_2021_06_011 crossref_primary_10_1016_j_tcb_2023_03_015 crossref_primary_10_1007_s00299_024_03187_x crossref_primary_10_1038_s41598_017_08257_7 crossref_primary_10_3390_genes9120622 crossref_primary_10_1016_j_molcel_2015_10_040 crossref_primary_10_1007_s10147_017_1145_7 crossref_primary_10_3390_molecules22030356 crossref_primary_10_1016_j_xpro_2025_103662 crossref_primary_10_1038_s41556_019_0293_6 crossref_primary_10_1371_journal_ppat_1013142 crossref_primary_10_1158_1078_0432_CCR_22_0875 crossref_primary_10_2217_fon_15_292 crossref_primary_10_3390_ijms21249715 crossref_primary_10_1101_gad_348858_121 crossref_primary_10_1038_onc_2015_135 crossref_primary_10_1093_nar_gkv880 crossref_primary_10_1038_s41375_019_0618_2 crossref_primary_10_1158_2159_8290_CD_23_0641 crossref_primary_10_1158_1535_7163_MCT_23_0402 crossref_primary_10_1016_j_devcel_2022_06_003 crossref_primary_10_1093_nar_gkab176 crossref_primary_10_1038_nrm_2017_67 crossref_primary_10_1186_s13046_022_02334_0 crossref_primary_10_1016_j_molcel_2016_10_032 crossref_primary_10_1016_j_ebiom_2015_12_012 crossref_primary_10_1002_jcp_25792 crossref_primary_10_1038_jid_2015_255 crossref_primary_10_1016_j_cell_2021_10_025 crossref_primary_10_1016_j_molcel_2023_01_003 crossref_primary_10_1038_cddis_2016_121 crossref_primary_10_1016_j_ccell_2019_05_001 crossref_primary_10_1093_nar_gkv573 crossref_primary_10_1038_nature13993 crossref_primary_10_1016_j_molcel_2018_07_011 crossref_primary_10_1016_j_molcel_2017_05_001 crossref_primary_10_1038_nrc3916 crossref_primary_10_1038_nrg_2017_46 crossref_primary_10_1093_nar_gkz1139 crossref_primary_10_1016_j_molcel_2015_07_029 crossref_primary_10_1038_s41467_018_05031_9 crossref_primary_10_1038_s41467_022_33027_z crossref_primary_10_1038_s41598_022_09308_4 crossref_primary_10_1111_febs_13574 crossref_primary_10_1158_0008_5472_CAN_14_3347 crossref_primary_10_1093_nar_gkad291 crossref_primary_10_3390_cells10102520 crossref_primary_10_1038_s41419_023_06042_1 crossref_primary_10_1038_srep43517 crossref_primary_10_1074_jbc_RA120_013780 crossref_primary_10_1093_nar_gkw791 crossref_primary_10_1038_s41568_018_0034_3 crossref_primary_10_1091_mbc_E15_05_0318 crossref_primary_10_4161_15384101_2014_964100 crossref_primary_10_3390_ijms18061138 crossref_primary_10_3390_cancers13123056 crossref_primary_10_3390_cells13171462 crossref_primary_10_1084_jem_20241432 crossref_primary_10_1146_annurev_genet_080320_031523 crossref_primary_10_1128_MCB_00090_21 crossref_primary_10_1097_CCO_0000000000000867 crossref_primary_10_3390_genes10040252 crossref_primary_10_3390_genes6020267 crossref_primary_10_1016_j_molcel_2020_12_034 crossref_primary_10_1038_s41467_019_11760_2 crossref_primary_10_15252_embr_202153639 crossref_primary_10_1073_pnas_2015654118 crossref_primary_10_1158_1541_7786_MCR_19_1051 crossref_primary_10_3390_genes7080051 crossref_primary_10_1038_s41467_023_39579_y crossref_primary_10_1042_BCJ20230284 crossref_primary_10_1128_JVI_01012_17 crossref_primary_10_1016_j_molcel_2025_04_006 crossref_primary_10_1016_j_mrfmmm_2020_111694 crossref_primary_10_1016_j_molcel_2015_07_030 crossref_primary_10_1038_ncomms11752 crossref_primary_10_1158_1078_0432_CCR_20_3358 crossref_primary_10_1007_s00018_017_2474_4 crossref_primary_10_1016_j_molcel_2022_08_007 crossref_primary_10_1016_j_molcel_2022_08_006 crossref_primary_10_1093_nar_gky1233 crossref_primary_10_3390_cells14100748 crossref_primary_10_4049_jimmunol_1801618 crossref_primary_10_1016_j_molcel_2016_03_006 crossref_primary_10_1038_s41467_017_02245_1 crossref_primary_10_1158_1078_0432_CCR_16_2273 crossref_primary_10_1093_abbs_gmw044 crossref_primary_10_1101_gad_290957_116 crossref_primary_10_1007_s00412_023_00807_5 crossref_primary_10_1093_abbs_gmw043 crossref_primary_10_1016_j_molcel_2015_06_007 crossref_primary_10_1080_10409238_2020_1813070 crossref_primary_10_1016_j_molcel_2017_05_015 crossref_primary_10_1038_s41467_018_03096_0 crossref_primary_10_1093_nar_gkaf573 crossref_primary_10_26508_lsa_202302111 crossref_primary_10_1038_ng_3790 crossref_primary_10_1016_j_ccell_2025_04_014 crossref_primary_10_1073_pnas_2206824119 crossref_primary_10_1016_j_devcel_2024_05_010 crossref_primary_10_1016_j_isci_2024_110373 crossref_primary_10_1038_s43018_022_00331_y crossref_primary_10_1016_j_jdermsci_2022_01_009 crossref_primary_10_1093_nar_gky525 crossref_primary_10_1007_s10637_015_0310_y crossref_primary_10_1016_j_ctrv_2018_09_003 crossref_primary_10_3390_ijms150712007 crossref_primary_10_1016_j_molcel_2017_11_035 crossref_primary_10_1182_bloodadvances_2017015214 crossref_primary_10_1016_j_ceb_2015_09_002 crossref_primary_10_3390_ijms242115907 crossref_primary_10_1080_13543784_2020_1783238 crossref_primary_10_1038_s41467_024_45139_9 crossref_primary_10_3390_ani15101419 crossref_primary_10_1038_s41594_023_01045_0 crossref_primary_10_1074_jbc_M116_765883 crossref_primary_10_1080_10985549_2023_2259739 crossref_primary_10_1016_j_dnarep_2016_11_002 crossref_primary_10_3390_genes10030232 crossref_primary_10_3390_genes11090990 crossref_primary_10_3390_biom5032123 crossref_primary_10_1371_journal_pone_0215696 crossref_primary_10_1038_s41598_024_81914_w crossref_primary_10_1016_j_jmb_2019_03_011 crossref_primary_10_1038_s41418_019_0403_9 crossref_primary_10_1016_j_dnarep_2019_102654 crossref_primary_10_1371_journal_pgen_1007541 crossref_primary_10_1016_j_mrfmmm_2014_08_004 crossref_primary_10_1016_j_molcel_2014_12_001 crossref_primary_10_1038_s41420_025_02383_2 crossref_primary_10_1016_j_dnarep_2019_102655 crossref_primary_10_1038_s41598_019_44771_6 crossref_primary_10_1016_j_yexcr_2018_08_025 crossref_primary_10_1158_0008_5472_CAN_14_2571 crossref_primary_10_1093_nar_gkaf278 crossref_primary_10_1016_j_celrep_2024_114214 crossref_primary_10_1038_onc_2014_276 crossref_primary_10_1002_em_22176 crossref_primary_10_1038_s41467_019_11095_y crossref_primary_10_3390_cancers13143464 crossref_primary_10_1016_j_molcel_2018_04_022 crossref_primary_10_1016_j_biopha_2024_117076 crossref_primary_10_1134_S0026893316030080 crossref_primary_10_3390_ijms241310488 crossref_primary_10_1016_j_molcel_2018_12_021 crossref_primary_10_1016_j_cell_2025_01_005 crossref_primary_10_3390_genes12071096 crossref_primary_10_1016_j_cels_2019_11_001 crossref_primary_10_1038_s41420_025_02306_1 crossref_primary_10_1038_s41467_024_46547_7 crossref_primary_10_1093_nar_gkw442 crossref_primary_10_1111_febs_16875 crossref_primary_10_1038_s41594_022_00871_y crossref_primary_10_3389_fonc_2018_00245 crossref_primary_10_1038_s43018_021_00225_5 crossref_primary_10_1007_s42764_022_00085_y crossref_primary_10_1038_srep30819 crossref_primary_10_1080_15384101_2017_1387696 crossref_primary_10_18632_oncotarget_12673 crossref_primary_10_1002_advs_202100753 crossref_primary_10_1128_MCB_01276_14 crossref_primary_10_1158_0008_5472_CAN_18_0618 crossref_primary_10_1016_j_mrgentox_2021_503422 crossref_primary_10_1073_pnas_2315242121 crossref_primary_10_1083_jcb_202009147 crossref_primary_10_1371_journal_pone_0213130 crossref_primary_10_3390_cancers13040795 crossref_primary_10_1158_2159_8290_CD_19_0789 crossref_primary_10_1038_s41523_021_00353_2 crossref_primary_10_1038_s41594_018_0075_z crossref_primary_10_3390_biomedicines10112775 crossref_primary_10_1002_hep_30529 crossref_primary_10_1016_j_pharmthera_2020_107518 crossref_primary_10_1016_j_jab_2017_10_008 crossref_primary_10_1016_S1875_5364_24_60694_1 crossref_primary_10_1158_0008_5472_CAN_18_2807 crossref_primary_10_1016_j_isci_2025_112757 crossref_primary_10_1091_mbc_E16_01_0025 crossref_primary_10_15252_embj_2021110145 crossref_primary_10_3390_ijms26020667 crossref_primary_10_1038_s41586_025_08815_4 crossref_primary_10_1158_0008_5472_CAN_22_3646 crossref_primary_10_3390_biology11060827 crossref_primary_10_1016_j_yexcr_2016_03_003 crossref_primary_10_1038_nature25507 crossref_primary_10_1016_j_yexcr_2014_09_030 crossref_primary_10_1016_j_cellsig_2022_110310 crossref_primary_10_1242_jcs_263749 crossref_primary_10_1016_j_ecoenv_2024_116032 crossref_primary_10_1200_EDBK_238473 crossref_primary_10_1016_j_molcel_2021_08_009 crossref_primary_10_1002_1878_0261_12497 crossref_primary_10_1172_JCI122622 crossref_primary_10_1002_cac2_12636 crossref_primary_10_1016_j_dnarep_2025_103831 crossref_primary_10_1016_j_yexcr_2014_09_019 crossref_primary_10_1038_s41594_020_0407_7 crossref_primary_10_1038_nrd4553 crossref_primary_10_1038_ncomms13887 crossref_primary_10_1016_j_dnarep_2025_103841 crossref_primary_10_1016_j_molcel_2025_06_002 crossref_primary_10_1038_s41418_020_00733_4 crossref_primary_10_1101_gad_348517_121 crossref_primary_10_1016_j_molcel_2025_06_001 crossref_primary_10_1073_pnas_2419712122 crossref_primary_10_1186_s13059_022_02638_6 crossref_primary_10_1073_pnas_2009899117 crossref_primary_10_1016_j_molcel_2015_09_011 crossref_primary_10_1016_j_cell_2018_07_011 crossref_primary_10_1016_j_chembiol_2019_12_005 crossref_primary_10_1101_gr_224527_117 crossref_primary_10_1126_sciadv_adr3673 crossref_primary_10_3389_fonc_2021_683688 crossref_primary_10_1186_1471_2105_15_308 crossref_primary_10_1136_gutjnl_2016_312623 crossref_primary_10_1038_ncomms6496 crossref_primary_10_1093_nar_gkz518 crossref_primary_10_1038_s41594_020_0418_4 crossref_primary_10_1080_15384101_2016_1152424 crossref_primary_10_1016_j_dnarep_2025_103824 crossref_primary_10_1101_gad_349431_122 crossref_primary_10_1111_febs_14377 crossref_primary_10_1002_ijc_35164 crossref_primary_10_1093_nar_gkw121 crossref_primary_10_1126_science_adl4606 crossref_primary_10_1016_j_cels_2018_05_011 crossref_primary_10_1073_pnas_2109334118 crossref_primary_10_15252_embj_2018101443 crossref_primary_10_1016_j_celrep_2024_114464 crossref_primary_10_1016_j_molcel_2020_07_010 crossref_primary_10_3389_fimmu_2024_1414376 crossref_primary_10_1158_0008_5472_CAN_20_0057 crossref_primary_10_1016_j_tcb_2019_06_005 crossref_primary_10_3390_molecules27113567 crossref_primary_10_1101_gad_297663_117 crossref_primary_10_1016_j_neo_2024_101092 crossref_primary_10_1371_journal_ppat_1011203 crossref_primary_10_1016_j_yexcr_2014_08_010 crossref_primary_10_15252_embj_201899154 crossref_primary_10_1038_nsmb_3251 crossref_primary_10_1093_nar_gkw132 crossref_primary_10_1158_0008_5472_CAN_24_1404 crossref_primary_10_1016_j_cell_2018_08_065 crossref_primary_10_1038_s41571_024_00863_5 crossref_primary_10_15252_embj_2019103838 crossref_primary_10_1002_1878_0261_13433 crossref_primary_10_1016_j_ccell_2019_02_004 crossref_primary_10_1038_s41598_024_70589_y crossref_primary_10_1111_php_12641 crossref_primary_10_7554_eLife_30523 |
| ContentType | Journal Article |
| Copyright | Copyright © 2013 Elsevier Inc. All rights reserved. |
| Copyright_xml | – notice: Copyright © 2013 Elsevier Inc. All rights reserved. |
| DBID | CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1016/j.cell.2013.10.043 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic MEDLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Biology |
| EISSN | 1097-4172 |
| ExternalDocumentID | 24267891 |
| Genre | Research Support, Non-U.S. Gov't Journal Article |
| GroupedDBID | --- --K -DZ -ET -~X 0R~ 0WA 1RT 1~5 29B 2FS 2WC 3EH 4.4 457 4G. 53G 5GY 5RE 5VS 62- 6J9 7-5 85S AAEDT AAEDW AAFWJ AAHBH AAIKJ AAKRW AAKUH AALRI AAMRU AAQFI AAVLU AAXUO AAYJJ AAYWO ABCQX ABDGV ABJNI ABMAC ABOCM ACGFO ACGFS ACNCT ACVFH ADBBV ADCNI ADEZE ADVLN ADXHL AEFWE AENEX AEUPX AEXQZ AFPUW AFTJW AGCQF AGHFR AGHSJ AGKMS AHHHB AIDAL AIGII AITUG AKAPO AKBMS AKRWK AKYEP ALMA_UNASSIGNED_HOLDINGS AMRAJ APXCP ASPBG AVWKF AZFZN BAWUL CGR CS3 CUY CVF DIK DU5 E3Z EBS ECM EFKBS EIF EJD F5P FCP FDB FIRID HH5 IH2 IHE IXB J1W JIG K-O KOO KQ8 L7B LX5 M3Z M41 N9A NPM O-L O9- OK1 P2P RIG RNS ROL RPZ SCP SDG SDP SES SSZ TAE TN5 TR2 TWZ UKR UPT WH7 YYQ YZZ ZCA 7X8 |
| ID | FETCH-LOGICAL-c453t-cd4c94e83d20e21d1e929ef989f53d81425a697760425b1e38277b860e7628ed2 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 693 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000327500600013&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1097-4172 |
| IngestDate | Thu Oct 02 07:00:28 EDT 2025 Mon Jul 21 06:03:59 EDT 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 5 |
| Language | English |
| License | Copyright © 2013 Elsevier Inc. All rights reserved. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c453t-cd4c94e83d20e21d1e929ef989f53d81425a697760425b1e38277b860e7628ed2 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| OpenAccessLink | http://www.cell.com/article/S0092867413013615/pdf |
| PMID | 24267891 |
| PQID | 1461869436 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_1461869436 pubmed_primary_24267891 |
| PublicationCentury | 2000 |
| PublicationDate | 2013-11-21 |
| PublicationDateYYYYMMDD | 2013-11-21 |
| PublicationDate_xml | – month: 11 year: 2013 text: 2013-11-21 day: 21 |
| PublicationDecade | 2010 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Cell |
| PublicationTitleAlternate | Cell |
| PublicationYear | 2013 |
| References | Cell. 2014 Jan 16;156(1-2):374 24267882 - Cell. 2013 Nov 21;155(5):979-80 |
| References_xml | – reference: 24267882 - Cell. 2013 Nov 21;155(5):979-80 – reference: - Cell. 2014 Jan 16;156(1-2):374 |
| SSID | ssj0008555 |
| Score | 2.6230059 |
| Snippet | ATR, activated by replication stress, protects replication forks locally and suppresses origin firing globally. Here, we show that these functions of ATR are... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 1088 |
| SubjectTerms | Ataxia Telangiectasia Mutated Proteins - metabolism Cell Line, Tumor Chromatin - chemistry Chromatin - metabolism DNA Damage - drug effects DNA Replication Genomic Instability Humans Neoplasms - drug therapy Protein Kinase Inhibitors - pharmacology Protein Kinase Inhibitors - therapeutic use Replication Origin Replication Protein A - metabolism |
| Title | ATR prohibits replication catastrophe by preventing global exhaustion of RPA |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/24267891 https://www.proquest.com/docview/1461869436 |
| Volume | 155 |
| WOSCitedRecordID | wos000327500600013&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV07T8MwELaAgsTC-1FeMhJrIImd2J5QhagYSlVVReoW1fGZdklKExD99_iSFCYkJJZMThRd7s5fznffR8iNsAyqiZ5UK-XxMAw8HbifFY3g2AA4p6nY9Xui35fjsRo0Bbeiaatc5cQqUZs8xRr5HepPy1hxFt_P3zxUjcLT1UZCY520mIMy6NVi_MMWLqNK9RQPWT3udupmaKbu78LCOLZ2sVvs7sKpnd8gZrXVdHf_-5J7ZKcBmbRTe8U-WYPsgGzVspPLQ9LrjIbUPXk607OyoAv4PsOmWM0pygWSDVC9dItqgqfsldbMIRQ-p8gUhGtzS4eDzhF56T6OHp68RlXBS3nESi81PFUcJDOhD2FgAnAICaySykbMyMAF8SR2qDDGcNYBMBkKoWXsg8ubEkx4TDayPINTQqOJhkikUuiJ4txwrXwrrA-pb42MtW6T65WZEue1aPFJBvl7kfwYqk1Oalsn85peI0HQIKQKzv5w9znZxk-Iw4FhcEFa1sUsXJLN9KOcFYuryh3ctT94_gLPgL6o |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=ATR+prohibits+replication+catastrophe+by+preventing+global+exhaustion+of+RPA&rft.jtitle=Cell&rft.au=Toledo%2C+Luis+Ignacio&rft.au=Altmeyer%2C+Matthias&rft.au=Rask%2C+Maj-Britt&rft.au=Lukas%2C+Claudia&rft.date=2013-11-21&rft.issn=1097-4172&rft.eissn=1097-4172&rft.volume=155&rft.issue=5&rft.spage=1088&rft_id=info:doi/10.1016%2Fj.cell.2013.10.043&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1097-4172&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1097-4172&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1097-4172&client=summon |