RNF168 ubiquitinates K13-15 on H2A/H2AX to drive DNA damage signaling

Ubiquitin-dependent signaling during the DNA damage response (DDR) to double-strand breaks (DSBs) is initiated by two E3 ligases, RNF8 and RNF168, targeting histone H2A and H2AX. RNF8 is the first ligase recruited to the damage site, and RNF168 follows RNF8-dependent ubiquitination. This suggests th...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Cell Jg. 150; H. 6; S. 1182
Hauptverfasser:	Mattiroli, Francesca, Vissers, Joseph H A, van Dijk, Willem J, Ikpa, Pauline, Citterio, Elisabetta, Vermeulen, Wim, Marteijn, Jurgen A, Sixma, Titia K
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States 14.09.2012
Schlagworte:	Amino Acid Sequence DNA-Binding Proteins - chemistry DNA-Binding Proteins - metabolism Histones - chemistry Histones - metabolism Humans Lysine - metabolism Models, Molecular Molecular Sequence Data Nucleosomes - chemistry Nucleosomes - metabolism Protein Structure, Tertiary Scattering, Small Angle Ubiquitin-Protein Ligases - chemistry Ubiquitin-Protein Ligases - metabolism X-Ray Diffraction
ISSN:	1097-4172, 1097-4172
Online-Zugang:	Weitere Angaben
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Abstract	Ubiquitin-dependent signaling during the DNA damage response (DDR) to double-strand breaks (DSBs) is initiated by two E3 ligases, RNF8 and RNF168, targeting histone H2A and H2AX. RNF8 is the first ligase recruited to the damage site, and RNF168 follows RNF8-dependent ubiquitination. This suggests that RNF8 initiates H2A/H2AX ubiquitination with K63-linked ubiquitin chains and RNF168 extends them. Here, we show that RNF8 is inactive toward nucleosomal H2A, whereas RNF168 catalyzes the monoubiquitination of the histones specifically on K13-15. Structure-based mutagenesis of RNF8 and RNF168 RING domains shows that a charged residue determines whether nucleosomal proteins are recognized. We find that K63 ubiquitin chains are conjugated to RNF168-dependent H2A/H2AX monoubiquitination at K13-15 and not on K118-119. Using a mutant of RNF168 unable to target histones but still catalyzing ubiquitin chains at DSBs, we show that ubiquitin chains per se are insufficient for signaling, but RNF168 target ubiquitination is required for DDR.
AbstractList	Ubiquitin-dependent signaling during the DNA damage response (DDR) to double-strand breaks (DSBs) is initiated by two E3 ligases, RNF8 and RNF168, targeting histone H2A and H2AX. RNF8 is the first ligase recruited to the damage site, and RNF168 follows RNF8-dependent ubiquitination. This suggests that RNF8 initiates H2A/H2AX ubiquitination with K63-linked ubiquitin chains and RNF168 extends them. Here, we show that RNF8 is inactive toward nucleosomal H2A, whereas RNF168 catalyzes the monoubiquitination of the histones specifically on K13-15. Structure-based mutagenesis of RNF8 and RNF168 RING domains shows that a charged residue determines whether nucleosomal proteins are recognized. We find that K63 ubiquitin chains are conjugated to RNF168-dependent H2A/H2AX monoubiquitination at K13-15 and not on K118-119. Using a mutant of RNF168 unable to target histones but still catalyzing ubiquitin chains at DSBs, we show that ubiquitin chains per se are insufficient for signaling, but RNF168 target ubiquitination is required for DDR.Ubiquitin-dependent signaling during the DNA damage response (DDR) to double-strand breaks (DSBs) is initiated by two E3 ligases, RNF8 and RNF168, targeting histone H2A and H2AX. RNF8 is the first ligase recruited to the damage site, and RNF168 follows RNF8-dependent ubiquitination. This suggests that RNF8 initiates H2A/H2AX ubiquitination with K63-linked ubiquitin chains and RNF168 extends them. Here, we show that RNF8 is inactive toward nucleosomal H2A, whereas RNF168 catalyzes the monoubiquitination of the histones specifically on K13-15. Structure-based mutagenesis of RNF8 and RNF168 RING domains shows that a charged residue determines whether nucleosomal proteins are recognized. We find that K63 ubiquitin chains are conjugated to RNF168-dependent H2A/H2AX monoubiquitination at K13-15 and not on K118-119. Using a mutant of RNF168 unable to target histones but still catalyzing ubiquitin chains at DSBs, we show that ubiquitin chains per se are insufficient for signaling, but RNF168 target ubiquitination is required for DDR. Ubiquitin-dependent signaling during the DNA damage response (DDR) to double-strand breaks (DSBs) is initiated by two E3 ligases, RNF8 and RNF168, targeting histone H2A and H2AX. RNF8 is the first ligase recruited to the damage site, and RNF168 follows RNF8-dependent ubiquitination. This suggests that RNF8 initiates H2A/H2AX ubiquitination with K63-linked ubiquitin chains and RNF168 extends them. Here, we show that RNF8 is inactive toward nucleosomal H2A, whereas RNF168 catalyzes the monoubiquitination of the histones specifically on K13-15. Structure-based mutagenesis of RNF8 and RNF168 RING domains shows that a charged residue determines whether nucleosomal proteins are recognized. We find that K63 ubiquitin chains are conjugated to RNF168-dependent H2A/H2AX monoubiquitination at K13-15 and not on K118-119. Using a mutant of RNF168 unable to target histones but still catalyzing ubiquitin chains at DSBs, we show that ubiquitin chains per se are insufficient for signaling, but RNF168 target ubiquitination is required for DDR.
Author	Ikpa, Pauline Mattiroli, Francesca Vermeulen, Wim van Dijk, Willem J Sixma, Titia K Vissers, Joseph H A Marteijn, Jurgen A Citterio, Elisabetta
Author_xml	– sequence: 1 givenname: Francesca surname: Mattiroli fullname: Mattiroli, Francesca organization: Division of Biochemistry and Center for Biomedical Genetics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands – sequence: 2 givenname: Joseph H A surname: Vissers fullname: Vissers, Joseph H A – sequence: 3 givenname: Willem J surname: van Dijk fullname: van Dijk, Willem J – sequence: 4 givenname: Pauline surname: Ikpa fullname: Ikpa, Pauline – sequence: 5 givenname: Elisabetta surname: Citterio fullname: Citterio, Elisabetta – sequence: 6 givenname: Wim surname: Vermeulen fullname: Vermeulen, Wim – sequence: 7 givenname: Jurgen A surname: Marteijn fullname: Marteijn, Jurgen A – sequence: 8 givenname: Titia K surname: Sixma fullname: Sixma, Titia K
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/22980979$$D View this record in MEDLINE/PubMed
BookMark	eNpNUE1Lw0AQXaRiP_QPeJA9ekk6M_ncY6mtFUsFUfAWNtlN2ZJs2mwi-O-NWMHDMI837z14M2Uj21jN2C2Cj4Dx_OAXuqp8AiQfUh8gumATBJF4ISY0-ofHbOrcAQDSKIqu2JhIpMNNTNjqdbfGOOV9bk696YyVnXb8GQMPI95YvqHFfJgP3jVcteZT84fdgitZy73mzuytrIzdX7PLUlZO35z3jL2vV2_Ljbd9eXxaLrZeEQZB56VKqAKTkgpQSktMQinjWFJSDgTKkmQeJEhCkQySQMSp1tFgEEEuClEWJc3Y_W_usW1OvXZdVhv38wRpddO7DCFEAEKCQXp3lvZ5rVV2bE0t26_srzp9A1KTWuI
CitedBy_id	crossref_primary_10_3390_jcm8091408 crossref_primary_10_1038_ncomms4291 crossref_primary_10_1007_s40610_015_0005_3 crossref_primary_10_1016_j_jbc_2023_105043 crossref_primary_10_1002_pro_5229 crossref_primary_10_1016_j_molcel_2017_08_021 crossref_primary_10_1016_j_jmb_2017_05_012 crossref_primary_10_1016_j_bbagrm_2023_194944 crossref_primary_10_1007_s42764_019_00007_5 crossref_primary_10_1084_jem_20131436 crossref_primary_10_1158_0008_5472_CAN_20_1248 crossref_primary_10_1083_jcb_202303141 crossref_primary_10_1126_science_1248024 crossref_primary_10_15252_emmm_201505891 crossref_primary_10_3389_fphys_2019_00835 crossref_primary_10_1111_nph_18787 crossref_primary_10_3390_ijms22168850 crossref_primary_10_1016_j_tcb_2013_09_003 crossref_primary_10_1038_ncomms10292 crossref_primary_10_1016_j_molcel_2013_01_017 crossref_primary_10_1038_s41417_021_00302_y crossref_primary_10_1016_j_lfs_2024_122912 crossref_primary_10_1016_j_bbamcr_2013_06_027 crossref_primary_10_1038_nature18951 crossref_primary_10_1038_onc_2013_60 crossref_primary_10_1016_j_it_2021_02_001 crossref_primary_10_1038_cr_2017_157 crossref_primary_10_1038_s41418_019_0397_3 crossref_primary_10_3724_abbs_2025008 crossref_primary_10_3390_ijms22168500 crossref_primary_10_1016_j_molcel_2013_01_006 crossref_primary_10_1016_j_tibs_2022_03_001 crossref_primary_10_1016_j_dnarep_2024_103702 crossref_primary_10_1038_onc_2013_275 crossref_primary_10_1038_s41586_021_03716_8 crossref_primary_10_1093_nar_gky104 crossref_primary_10_3389_fgene_2016_00103 crossref_primary_10_1073_pnas_2322972121 crossref_primary_10_1038_ncomms15751 crossref_primary_10_3389_fcell_2022_932633 crossref_primary_10_1016_j_dnarep_2021_103192 crossref_primary_10_1155_2022_2422618 crossref_primary_10_1042_EBC20200007 crossref_primary_10_1038_s12276_022_00863_4 crossref_primary_10_1038_s41420_023_01762_x crossref_primary_10_3390_pathogens9060483 crossref_primary_10_1016_j_dnarep_2017_06_010 crossref_primary_10_1016_j_dnarep_2017_06_011 crossref_primary_10_3390_ijms20174093 crossref_primary_10_1038_s41418_023_01192_3 crossref_primary_10_1111_febs_14048 crossref_primary_10_7554_eLife_20922 crossref_primary_10_1038_s41420_024_02154_5 crossref_primary_10_1101_gad_307702_117 crossref_primary_10_1093_nar_gkx261 crossref_primary_10_15252_embr_201439434 crossref_primary_10_1146_annurev_cellbio_100617_062802 crossref_primary_10_1080_10409238_2019_1620676 crossref_primary_10_15252_embr_201438793 crossref_primary_10_1016_j_dnarep_2015_04_015 crossref_primary_10_1186_s13072_020_00371_7 crossref_primary_10_1093_nar_gkz138 crossref_primary_10_7554_eLife_38771 crossref_primary_10_1080_15384101_2017_1404210 crossref_primary_10_3390_biomedicines11092527 crossref_primary_10_1074_jbc_M116_715698 crossref_primary_10_1016_j_gene_2021_145670 crossref_primary_10_1038_s41467_019_12929_5 crossref_primary_10_1186_s12610_022_00179_3 crossref_primary_10_1134_S1607672920040079 crossref_primary_10_1074_jbc_M116_765602 crossref_primary_10_1016_j_molcel_2018_02_022 crossref_primary_10_3390_biom12070910 crossref_primary_10_1074_jbc_M114_599605 crossref_primary_10_1016_j_semcdb_2020_07_002 crossref_primary_10_1074_jbc_M114_601179 crossref_primary_10_1016_j_molcel_2019_03_005 crossref_primary_10_1093_nar_gkv1196 crossref_primary_10_3389_fgene_2017_00067 crossref_primary_10_1093_nar_gkz263 crossref_primary_10_1016_j_dnarep_2015_09_016 crossref_primary_10_3892_mmr_2017_7624 crossref_primary_10_1042_EBC20210094 crossref_primary_10_3892_or_2025_8947 crossref_primary_10_1038_nrm3822 crossref_primary_10_1093_nar_gkac843 crossref_primary_10_3389_fgene_2022_793884 crossref_primary_10_1038_s41392_024_01918_w crossref_primary_10_1016_j_molcel_2024_10_034 crossref_primary_10_1038_nsmb_2792 crossref_primary_10_3390_genes12060845 crossref_primary_10_1007_s42764_019_00004_8 crossref_primary_10_1016_j_biochi_2018_07_029 crossref_primary_10_1002_1873_3468_13583 crossref_primary_10_1096_fj_202002234R crossref_primary_10_1038_s41467_020_19202_0 crossref_primary_10_3390_biom6040047 crossref_primary_10_1038_s41594_020_00556_4 crossref_primary_10_1093_nar_gkac611 crossref_primary_10_3389_fcell_2022_909696 crossref_primary_10_3390_cells9071699 crossref_primary_10_1016_j_jmb_2017_05_029 crossref_primary_10_1038_s41420_024_01999_0 crossref_primary_10_1038_cr_2015_138 crossref_primary_10_3389_fcell_2020_00717 crossref_primary_10_1093_nar_gkae918 crossref_primary_10_1080_15384101_2015_1049087 crossref_primary_10_1038_s41598_017_16934_w crossref_primary_10_1016_j_semcdb_2021_11_006 crossref_primary_10_1016_j_yexcr_2021_112679 crossref_primary_10_1038_nrm3719 crossref_primary_10_1016_j_dnarep_2021_103140 crossref_primary_10_1530_REP_17_0153 crossref_primary_10_1016_j_dnarep_2021_103129 crossref_primary_10_1186_s13062_024_00484_z crossref_primary_10_1016_j_semcdb_2022_03_011 crossref_primary_10_1080_19491034_2016_1267092 crossref_primary_10_1242_jcs_122945 crossref_primary_10_3390_ijms22062976 crossref_primary_10_1007_s00335_017_9688_5 crossref_primary_10_1016_j_cca_2019_04_077 crossref_primary_10_1111_jcmm_13694 crossref_primary_10_1371_journal_pone_0144957 crossref_primary_10_3389_fmolb_2019_00051 crossref_primary_10_3390_cancers12061617 crossref_primary_10_1111_nph_14915 crossref_primary_10_1073_pnas_1504868112 crossref_primary_10_1002_ange_202002974 crossref_primary_10_1074_jbc_M114_626788 crossref_primary_10_3390_ijms21113762 crossref_primary_10_1126_science_ado3867 crossref_primary_10_1038_nsmb_2805 crossref_primary_10_1128_jvi_00201_23 crossref_primary_10_1038_s41416_019_0624_1 crossref_primary_10_1002_bies_201400104 crossref_primary_10_1038_s41467_018_05161_0 crossref_primary_10_1007_s40495_017_0099_9 crossref_primary_10_1083_jcb_202111050 crossref_primary_10_1038_s41467_024_49431_6 crossref_primary_10_1016_j_tig_2020_12_005 crossref_primary_10_1007_s11515_016_1435_x crossref_primary_10_1074_jbc_M114_624478 crossref_primary_10_1080_15384101_2015_1007785 crossref_primary_10_15252_embj_201695151 crossref_primary_10_1186_s13578_020_0380_1 crossref_primary_10_3389_fgene_2021_738230 crossref_primary_10_1007_s11427_016_5011_z crossref_primary_10_1093_nar_gkaa022 crossref_primary_10_1016_j_molcel_2014_01_030 crossref_primary_10_1021_jacs_2c06156 crossref_primary_10_1042_BCJ20200066 crossref_primary_10_1186_s12916_025_04247_z crossref_primary_10_1016_j_molcel_2016_05_027 crossref_primary_10_1038_emboj_2013_117 crossref_primary_10_1002_tox_23428 crossref_primary_10_1038_s41467_018_04649_z crossref_primary_10_1101_gad_271841_115 crossref_primary_10_1016_j_fct_2019_110745 crossref_primary_10_1016_j_dnarep_2021_103217 crossref_primary_10_1002_em_22623 crossref_primary_10_1016_j_dnarep_2021_103211 crossref_primary_10_1101_gad_264192_115 crossref_primary_10_1158_0008_5472_CAN_19_3033 crossref_primary_10_3389_fimmu_2014_00100 crossref_primary_10_1371_journal_ppat_1008514 crossref_primary_10_1128_MCB_01024_12 crossref_primary_10_3389_fgene_2016_00063 crossref_primary_10_1016_j_jid_2024_04_017 crossref_primary_10_3389_fgene_2016_00058 crossref_primary_10_1016_j_molcel_2015_03_023 crossref_primary_10_1158_0008_5472_CAN_22_4017 crossref_primary_10_3389_fmolb_2019_00079 crossref_primary_10_3390_cells9081853 crossref_primary_10_1093_nar_gkad631 crossref_primary_10_1038_s41598_017_15194_y crossref_primary_10_1111_cpr_13398 crossref_primary_10_15252_embj_201593499 crossref_primary_10_1038_s41580_019_0099_1 crossref_primary_10_1016_j_phrs_2019_104557 crossref_primary_10_1016_j_bbagrm_2024_195044 crossref_primary_10_1042_BST20190534 crossref_primary_10_1016_j_molcel_2016_05_004 crossref_primary_10_1073_pnas_1711158114 crossref_primary_10_1016_j_bbrc_2023_02_022 crossref_primary_10_1093_nar_gkv613 crossref_primary_10_1073_pnas_1320302111 crossref_primary_10_1080_15384101_2020_1758435 crossref_primary_10_1007_s00109_017_1561_1 crossref_primary_10_1002_mc_23819 crossref_primary_10_3389_fgene_2015_00282 crossref_primary_10_3389_fgene_2016_00122 crossref_primary_10_1158_1940_6207_CAPR_20_0470 crossref_primary_10_1007_s42764_024_00131_x crossref_primary_10_3390_cancers12010058 crossref_primary_10_15252_embj_201592595 crossref_primary_10_1242_jcs_183103 crossref_primary_10_1016_j_bbagrm_2024_195033 crossref_primary_10_1016_j_molcel_2021_05_010 crossref_primary_10_1002_advs_202403485 crossref_primary_10_1074_jbc_RA120_014349 crossref_primary_10_1074_jbc_M113_461699 crossref_primary_10_1371_journal_ppat_1008618 crossref_primary_10_1038_s41467_018_03895_5 crossref_primary_10_1002_ange_202408435 crossref_primary_10_1016_j_pharmthera_2021_108009 crossref_primary_10_1007_s00018_015_2129_2 crossref_primary_10_1016_j_chembiol_2021_04_008 crossref_primary_10_1038_s41586_019_1703_4 crossref_primary_10_1093_nar_gkad213 crossref_primary_10_1371_journal_ppat_1005102 crossref_primary_10_1016_j_biocel_2014_03_004 crossref_primary_10_1002_anie_202413651 crossref_primary_10_3390_ijms18122611 crossref_primary_10_1080_15384101_2016_1261227 crossref_primary_10_3390_cancers10090298 crossref_primary_10_1038_s41586_021_03776_w crossref_primary_10_1134_S0006297921140066 crossref_primary_10_1111_cas_13008 crossref_primary_10_1186_s12885_023_10506_0 crossref_primary_10_3389_fimmu_2018_00355 crossref_primary_10_1093_nar_gkaa154 crossref_primary_10_1038_nsmb_2702 crossref_primary_10_1016_j_bbcan_2024_189206 crossref_primary_10_1080_15384101_2015_1010918 crossref_primary_10_1016_j_bbagrm_2014_04_016 crossref_primary_10_1016_j_sbi_2016_11_016 crossref_primary_10_1002_cbic_201800432 crossref_primary_10_1038_s41467_019_09756_z crossref_primary_10_1093_nar_gkae756 crossref_primary_10_1093_nar_gkw1241 crossref_primary_10_1002_embr_201338369 crossref_primary_10_1093_procel_pwad045 crossref_primary_10_1007_s12013_013_9635_3 crossref_primary_10_1038_nrm_2016_58 crossref_primary_10_3389_fcell_2022_928113 crossref_primary_10_1038_s41418_025_01472_0 crossref_primary_10_1093_nar_gkad793 crossref_primary_10_3389_fimmu_2017_01683 crossref_primary_10_3390_cancers12010183 crossref_primary_10_1083_jcb_201302092 crossref_primary_10_1038_onc_2016_392 crossref_primary_10_1093_toxres_tfab030 crossref_primary_10_1002_1873_3468_14294 crossref_primary_10_1016_j_molcel_2016_03_031 crossref_primary_10_1002_1873_3468_15024 crossref_primary_10_1128_JVI_00262_18 crossref_primary_10_1051_jbio_2021006 crossref_primary_10_1016_j_molcel_2017_04_009 crossref_primary_10_1016_j_mrrev_2017_09_003 crossref_primary_10_3390_cancers17060949 crossref_primary_10_1007_s11010_024_05131_9 crossref_primary_10_1007_s00425_015_2451_9 crossref_primary_10_1172_JCI120401 crossref_primary_10_3390_ijms14022355 crossref_primary_10_1016_j_gpb_2018_07_004 crossref_primary_10_1101_gad_344044_120 crossref_primary_10_1371_journal_pone_0169054 crossref_primary_10_1016_j_molcel_2020_12_021 crossref_primary_10_1093_nar_gkac160 crossref_primary_10_3390_cells10102563 crossref_primary_10_1038_nm_3739 crossref_primary_10_1038_s41388_025_03454_5 crossref_primary_10_1016_j_mrfmmm_2017_04_003 crossref_primary_10_1074_jbc_M114_612796 crossref_primary_10_1186_s13072_019_0294_5 crossref_primary_10_1146_annurev_physiol_021115_105127 crossref_primary_10_1038_s41594_018_0083_z crossref_primary_10_3390_ijms23179610 crossref_primary_10_1093_nar_gku421 crossref_primary_10_1038_s41467_021_25346_4 crossref_primary_10_15252_embr_201540620 crossref_primary_10_4161_cc_27303 crossref_primary_10_1038_s41392_024_01800_9 crossref_primary_10_1016_j_mcpro_2023_100548 crossref_primary_10_1038_s41556_018_0071_x crossref_primary_10_1172_JCI120518 crossref_primary_10_7554_eLife_87086 crossref_primary_10_1074_jbc_M113_459917 crossref_primary_10_1016_j_molcel_2017_04_013 crossref_primary_10_1016_j_jbc_2025_108300 crossref_primary_10_1093_nar_gkv528 crossref_primary_10_1101_gad_332395_119 crossref_primary_10_7554_eLife_23872 crossref_primary_10_1093_abbs_gmx055 crossref_primary_10_1259_bjr_20130685 crossref_primary_10_15252_embj_2020104542 crossref_primary_10_1016_j_molcel_2014_06_028 crossref_primary_10_3390_ijms18081715 crossref_primary_10_1093_nar_gkaf897 crossref_primary_10_1038_s41467_020_16307_4 crossref_primary_10_1016_j_taap_2018_07_007 crossref_primary_10_1093_nar_gkab293 crossref_primary_10_1073_pnas_1614120113 crossref_primary_10_1177_11795549241281932 crossref_primary_10_1042_BJ20141571 crossref_primary_10_1038_s41594_023_01096_3 crossref_primary_10_1038_s41467_021_24298_z crossref_primary_10_1038_s41576_022_00468_7 crossref_primary_10_1242_jcs_138891 crossref_primary_10_1016_j_tig_2017_12_011 crossref_primary_10_1093_nar_gkv336 crossref_primary_10_3390_cells8020165 crossref_primary_10_4161_cc_26640 crossref_primary_10_1016_j_tcb_2014_01_005 crossref_primary_10_1111_jcmm_14063 crossref_primary_10_1038_srep18940 crossref_primary_10_3389_freae_2024_1445765 crossref_primary_10_1139_bcb_2016_0017 crossref_primary_10_1016_j_molcel_2018_07_011 crossref_primary_10_3390_cells14040307 crossref_primary_10_1093_nar_gkae499 crossref_primary_10_3390_epigenomes9030029 crossref_primary_10_15252_embj_2019102361 crossref_primary_10_3390_cancers10030059 crossref_primary_10_1074_jbc_R115_667931 crossref_primary_10_1083_jcb_201911130 crossref_primary_10_1083_jcb_201506099 crossref_primary_10_1371_journal_pone_0084899 crossref_primary_10_1093_nar_gkz824 crossref_primary_10_1038_s41467_020_19504_3 crossref_primary_10_1101_gad_333237_119 crossref_primary_10_3390_cells11152404 crossref_primary_10_3390_ijms24043248 crossref_primary_10_4161_cc_28707 crossref_primary_10_1038_s41598_017_13036_5 crossref_primary_10_1074_jbc_RA118_007009 crossref_primary_10_1002_bies_201600094 crossref_primary_10_1016_j_fsi_2025_110244 crossref_primary_10_3389_fcell_2022_968398 crossref_primary_10_1042_BJ20121702 crossref_primary_10_3390_cells13171462 crossref_primary_10_1371_journal_pone_0111177 crossref_primary_10_1016_j_biopha_2024_116747 crossref_primary_10_1073_pnas_2202970119 crossref_primary_10_1002_tox_23985 crossref_primary_10_1158_0008_5472_CAN_13_2131 crossref_primary_10_1016_j_gde_2021_05_006 crossref_primary_10_1042_BCJ20180883 crossref_primary_10_1073_pnas_1809592115 crossref_primary_10_1007_s42764_020_00026_7 crossref_primary_10_1042_BCJ20230284 crossref_primary_10_1016_j_bbcan_2022_188716 crossref_primary_10_3390_biom10111503 crossref_primary_10_3390_ijms23158187 crossref_primary_10_2217_fvl_2019_0015 crossref_primary_10_3389_fchem_2020_00111 crossref_primary_10_3389_fcimb_2022_901994 crossref_primary_10_1093_jb_mvab010 crossref_primary_10_1111_febs_15857 crossref_primary_10_1158_0008_5472_CAN_13_3109 crossref_primary_10_1074_jbc_M116_758854 crossref_primary_10_3390_genes10010067 crossref_primary_10_1016_j_molcel_2017_05_015 crossref_primary_10_1016_j_ymeth_2014_07_006 crossref_primary_10_1038_s41589_024_01750_x crossref_primary_10_1093_nar_gkaf574 crossref_primary_10_3390_v5071758 crossref_primary_10_1158_1541_7786_MCR_17_0688 crossref_primary_10_1002_j_2040_4603_2021_tb00170_x crossref_primary_10_1016_j_mrrev_2012_10_001 crossref_primary_10_1016_j_yexcr_2014_08_025 crossref_primary_10_1038_cdd_2016_58 crossref_primary_10_1080_14756366_2025_2489720 crossref_primary_10_1080_15548627_2017_1317427 crossref_primary_10_1146_annurev_biochem_061809_174504 crossref_primary_10_1038_s41467_024_49071_w crossref_primary_10_3390_ijms24087656 crossref_primary_10_3390_ijms25010204 crossref_primary_10_4161_15384101_2014_977067 crossref_primary_10_1186_s12896_020_00650_x crossref_primary_10_1002_ange_202413651 crossref_primary_10_3389_freae_2023_1238154 crossref_primary_10_1038_ncomms10201 crossref_primary_10_1016_j_jmb_2024_168442 crossref_primary_10_1038_nrm3659 crossref_primary_10_3390_cells9020466 crossref_primary_10_1074_jbc_M113_469783 crossref_primary_10_1038_s41419_023_05656_9 crossref_primary_10_3390_genes13122390 crossref_primary_10_1093_jrr_rrw027 crossref_primary_10_1002_anie_202408435 crossref_primary_10_1038_s41467_025_61768_0 crossref_primary_10_2217_epi_2023_0234 crossref_primary_10_1016_j_molcel_2023_12_036 crossref_primary_10_1093_nar_gkx565 crossref_primary_10_1016_j_molmed_2021_04_010 crossref_primary_10_1038_ncomms12638 crossref_primary_10_1016_j_molcel_2020_09_017 crossref_primary_10_1002_advs_202000157 crossref_primary_10_1038_s41467_017_02345_y crossref_primary_10_1038_s41388_017_0092_0 crossref_primary_10_3389_fcell_2025_1548946 crossref_primary_10_3389_fphar_2023_1137151 crossref_primary_10_3390_v13101998 crossref_primary_10_3892_ijmm_2022_5145 crossref_primary_10_1073_pnas_1604277113 crossref_primary_10_2147_OTT_S463217 crossref_primary_10_4161_cc_23104 crossref_primary_10_1016_j_dnarep_2019_102686 crossref_primary_10_1038_s41576_024_00759_1 crossref_primary_10_1042_EBC20190094 crossref_primary_10_1080_15384101_2019_1690231 crossref_primary_10_1158_0008_5472_CAN_16_0723 crossref_primary_10_3389_fgene_2022_887088 crossref_primary_10_1073_pnas_1906102116 crossref_primary_10_1016_j_jmb_2015_11_021 crossref_primary_10_1080_15384101_2017_1361066 crossref_primary_10_1007_s42764_024_00139_3 crossref_primary_10_1016_j_mrfmmm_2013_07_007 crossref_primary_10_1080_09553002_2018_1516911 crossref_primary_10_2174_0929867324666170921101947 crossref_primary_10_1016_j_mrfmmm_2013_07_004 crossref_primary_10_3389_fmolb_2021_655786 crossref_primary_10_1016_j_molcel_2018_12_010 crossref_primary_10_1038_s41598_021_88988_w crossref_primary_10_1007_s00018_021_03984_7 crossref_primary_10_15252_embj_2023113565 crossref_primary_10_1007_s00018_019_03299_8 crossref_primary_10_1093_nar_gkz726 crossref_primary_10_1158_0008_5472_CAN_22_1535 crossref_primary_10_1158_0008_5472_CAN_14_2796 crossref_primary_10_15252_embr_201541685 crossref_primary_10_3390_ijms21218039 crossref_primary_10_1016_j_gde_2012_11_001 crossref_primary_10_1038_nature12318 crossref_primary_10_1038_s44319_024_00306_3 crossref_primary_10_3389_fchem_2018_00019 crossref_primary_10_1016_j_tibs_2019_12_010 crossref_primary_10_1093_nar_gkz897 crossref_primary_10_1038_s41467_025_56974_9 crossref_primary_10_1038_s41556_017_0033_8 crossref_primary_10_1631_jzus_B2000309 crossref_primary_10_3390_cells12060886 crossref_primary_10_1186_s13072_021_00385_9 crossref_primary_10_1631_jzus_B2000306 crossref_primary_10_15252_embj_2018101341 crossref_primary_10_1038_s41388_023_02667_w crossref_primary_10_1016_j_gene_2022_146599 crossref_primary_10_1016_j_tig_2019_02_003 crossref_primary_10_1158_0008_5472_CAN_17_2143 crossref_primary_10_3389_fgene_2020_600615 crossref_primary_10_3390_ijms25084393 crossref_primary_10_1038_s43018_021_00200_0 crossref_primary_10_1042_BCJ20240124 crossref_primary_10_1002_cbic_202000459 crossref_primary_10_1371_journal_pone_0102968 crossref_primary_10_1038_nature15401 crossref_primary_10_1016_j_clon_2014_02_004 crossref_primary_10_1016_j_coph_2024_102496 crossref_primary_10_1016_j_molcel_2015_09_011 crossref_primary_10_3389_fgene_2021_747734 crossref_primary_10_3390_biom14080993 crossref_primary_10_1038_s41467_017_02653_3 crossref_primary_10_1073_pnas_1308888110 crossref_primary_10_1007_s42764_022_00076_z crossref_primary_10_1016_j_molcel_2025_07_013 crossref_primary_10_1101_gad_289439_116 crossref_primary_10_1371_journal_pgen_1008550 crossref_primary_10_1016_j_biocel_2014_09_027 crossref_primary_10_4161_cc_26814 crossref_primary_10_1128_MCB_00847_15 crossref_primary_10_1073_pnas_2320804121 crossref_primary_10_1038_s41598_017_03385_6 crossref_primary_10_18632_oncotarget_4584 crossref_primary_10_1007_s42764_021_00042_1 crossref_primary_10_3390_molecules28031417 crossref_primary_10_1371_journal_pgen_1004178 crossref_primary_10_1186_s12929_021_00743_5 crossref_primary_10_3390_ijms25031676 crossref_primary_10_1021_acs_biochem_5c00114 crossref_primary_10_3390_biom5043396 crossref_primary_10_1080_15384101_2018_1542899 crossref_primary_10_1098_rsob_150018 crossref_primary_10_1002_anie_202002974 crossref_primary_10_1016_j_bioorg_2025_108524
ContentType	Journal Article
Copyright	Copyright © 2012 Elsevier Inc. All rights reserved.
Copyright_xml	– notice: Copyright © 2012 Elsevier Inc. All rights reserved.
DBID	CGR CUY CVF ECM EIF NPM 7X8
DOI	10.1016/j.cell.2012.08.005
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	22980979
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 9M8 AACTN AAEDT AAEDW AAFWJ AAHBH AAIKJ AAKRW AAKUH AALRI AAMRU AAQFI AAVLU AAXUO AAYJJ ABCQX ABJNI ABMAC ABOCM ABTAH ACGFO ACGFS ACNCT ADBBV ADEZE ADVLN AEFWE AENEX AEXQZ AFTJW AGHFR AGHSJ AGKMS AHHHB AIDAL AITUG AKAPO AKRWK ALMA_UNASSIGNED_HOLDINGS AMRAJ ASPBG AVWKF AZFZN BAWUL CGR CS3 CUY CVF DIK DU5 E3Z EBS ECM EIF EJD F5P FCP FDB FIRID HH5 HZ~ 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 ZY4 7X8 AAYWO ABDGV ACVFH ADCNI ADXHL AEUPX AFPUW AIGII AKBMS AKYEP APXCP EFKBS
ID	FETCH-LOGICAL-c433t-8d9dc17f2c0ddea174aa66a27fc0d1af2ab37129d2a373968ee5dc193b9c9fcf2
IEDL.DBID	7X8
ISICitedReferencesCount	521
ISICitedReferencesURI	http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000308928100012&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	Sun Sep 28 12:04:45 EDT 2025 Thu Apr 03 06:59:54 EDT 2025
IsDoiOpenAccess	false
IsOpenAccess	true
IsPeerReviewed	true
IsScholarly	true
Issue	6
Language	English
License	Copyright © 2012 Elsevier Inc. All rights reserved.
LinkModel	DirectLink
MergedId	FETCHMERGED-LOGICAL-c433t-8d9dc17f2c0ddea174aa66a27fc0d1af2ab37129d2a373968ee5dc193b9c9fcf2
Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
OpenAccessLink	https://www.cell.com/article/S0092867412010008/pdf
PMID	22980979
PQID	1041002120
PQPubID	23479
ParticipantIDs	proquest_miscellaneous_1041002120 pubmed_primary_22980979
PublicationCentury	2000
PublicationDate	2012-09-14
PublicationDateYYYYMMDD	2012-09-14
PublicationDate_xml	– month: 09 year: 2012 text: 2012-09-14 day: 14
PublicationDecade	2010
PublicationPlace	United States
PublicationPlace_xml	– name: United States
PublicationTitle	Cell
PublicationTitleAlternate	Cell
PublicationYear	2012
SSID	ssj0008555
Score	2.5871022
Snippet	Ubiquitin-dependent signaling during the DNA damage response (DDR) to double-strand breaks (DSBs) is initiated by two E3 ligases, RNF8 and RNF168, targeting...
SourceID	proquest pubmed
SourceType	Aggregation Database Index Database
StartPage	1182
SubjectTerms	Amino Acid Sequence DNA-Binding Proteins - chemistry DNA-Binding Proteins - metabolism Histones - chemistry Histones - metabolism Humans Lysine - metabolism Models, Molecular Molecular Sequence Data Nucleosomes - chemistry Nucleosomes - metabolism Protein Structure, Tertiary Scattering, Small Angle Ubiquitin-Protein Ligases - chemistry Ubiquitin-Protein Ligases - metabolism X-Ray Diffraction
Title	RNF168 ubiquitinates K13-15 on H2A/H2AX to drive DNA damage signaling
URI	https://www.ncbi.nlm.nih.gov/pubmed/22980979 https://www.proquest.com/docview/1041002120
Volume	150
WOSCitedRecordID	wos000308928100012&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/eLvHCXMwpV1LS8QwEA7qKnjx_VhfRPBabJKmaU6y6C4LallEobeSJin0YLuPruC_d9J22ZMgeGgPhUCYzOPr5JsZhO6EgwEqV54bF-e5CAF-kAaeZlpyDXjX8qZQ-EXEcZQkctIl3BYdrXLlExtHbSrtcuRg3QFp-pH7D9OZ56ZGudvVboTGJuoxgDKO0iWSdbfwiDdTT90lK2xD0K5opuV3ucS4o3bRpoWnz3-HmE2oGe3_d5MHaK8DmXjQasUh2rDlEdppx05-H6PhWzwiYYSXWTFbFnVROryJnwnzCMdVicd0cA9PgusKmzm4Q_wUD7BRn-B7sCN8KFfDfoI-RsP3x7HXjVPwdMBY7UVGGk1ETrUPPk3Br4hSYaioyOEDUTlVGRMQ_g1VTDAZRtZyWCBZJrXMdU5P0VZZlfYcYWs1V0Rx6mc2CKyfSWJYIDMtKRg5MX10u5JPCurqRK1KWy0X6VpCfXTWCjmdtn01UkplBEclL_6w-hLturNzzA0SXKFeDsZqr9G2_qqLxfym0QN4x5PXHwdLuKA
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=RNF168+ubiquitinates+K13-15+on+H2A%2FH2AX+to+drive+DNA+damage+signaling&rft.jtitle=Cell&rft.au=Mattiroli%2C+Francesca&rft.au=Vissers%2C+Joseph+H+A&rft.au=van+Dijk%2C+Willem+J&rft.au=Ikpa%2C+Pauline&rft.date=2012-09-14&rft.eissn=1097-4172&rft.volume=150&rft.issue=6&rft.spage=1182&rft_id=info:doi/10.1016%2Fj.cell.2012.08.005&rft_id=info%3Apmid%2F22980979&rft_id=info%3Apmid%2F22980979&rft.externalDocID=22980979
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