The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks
Abstract
The mechanisms by which eukaryotic cells sense DNA double-strand breaks (DSBs) in order to initiate checkpoint responses are poorly understood. 53BP1 is a conserved checkpoint protein with properties of a DNA DSB sensor. Here, we solved the structure of the domain of 53BP1 that recruits it to sites of DSBs. This domain consists of two tandem tudor folds with a deep pocket at their interface formed by residues conserved in the budding yeast Rad9 and fission yeast Rhp9/Crb2 orthologues. In vitro, the 53BP1 tandem tudor domain bound histone H3 methylated on Lys 79 using residues that form the walls of the pocket; these residues were also required for recruitment of 53BP1 to DSBs. Suppression of DOT1L, the enzyme that methylates Lys 79 of histone H3, also inhibited recruitment of 53BP1 to DSBs. Because methylation of histone H3 Lys 79 was unaltered in response to DNA damage, we propose that 53BP1 senses DSBs indirectly through changes in higher-order chromatin structure that expose the 53BP1 binding site.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“dual inhibitors of LSD1 and HDACs, which provide more effective and sustained inhibition of the REST corepressor 1 (CoREST) complex than existing class I HDAC inhibitors”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [207]
Citations
Cites
Crystal structure of the nucleosome core particle at 2.8 Å resolution
Luger, K., Mäder, A. W., Richmond, R. K., Sargent, D. F., & Richmond, T. J. (1997) · Nature · doi:10.1038/38444 · Cited by 9,466
DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
Bakkenist, C. J., & Kastan, M. B. (2003) · Nature · doi:10.1038/nature01368 · Cited by 3,466
Megabase Chromatin Domains Involved in DNA Double-Strand Breaks in Vivo
Rogakou, E. P., Boon, C., Redon, C., & Bonner, W. M. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.146.5.905 · Cited by 2,422
The RAD9 Gene Controls the Cell Cycle Response to DNA Damage in Saccharomyces cerevisiae
Weinert, T. A., & Hartwell, L. H. (1988) · Science · doi:10.1126/science.3291120 · Cited by 1,171
Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks
Celeste, A., Fernandez-Capetillo, O., Kruhlak, M. J., Pilch, D. R., Staudt, D. W., Lee, A., Bonner, R. F., Bonner, W. M., & Nussenzweig, A. (2003) · Nature Cell Biology · doi:10.1038/ncb1004 · Cited by 989
Schultz, L. B., Chehab, N. H., Malikzay, A., & Halazonetis, T. D. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.151.7.1381 · Cited by 916
Self-citationHistone methylation in transcriptional control
Kouzarides, T. (2002) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(02)00287-3 · Cited by 908
Methylation of H3-Lysine 79 Is Mediated by a New Family of HMTases without a SET Domain
Feng, Q. F., Wang, H., Ng, H., Erdjument‐Bromage, H., Tempst, P., Struhl, K., & Zhang, Y. (2002) · Current Biology · doi:10.1016/s0960-9822(02)00901-6 · Cited by 897
Dot1p Modulates Silencing in Yeast by Methylation of the Nucleosome Core
van Leeuwen, F., Gafken, P. R., & Gottschling, D. E. (2002) · Cell · doi:10.1016/s0092-8674(02)00759-6 · Cited by 853
Interaction of Human DNA Polymerase η with Monoubiquitinated PCNA
Kannouche, P. L., Wing, J., & Lehmann, A. R. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00259-x · Cited by 845
Flagged first, then by citations
Cited by
Sorted by citations
Items 301–400 of 883
Impact of Histone H4 Lysine 20 Methylation on 53BP1 Responses to Chromosomal Double Strand Breaks
Hartlerode, A. J., Guan, Y., Rajendran, A., Ura, K., Schotta, G., Xie, A., Shah, J. V., & Scully, R. (2012) · PLoS ONE · doi:10.1371/journal.pone.0049211 · Cited by 70
“interaction with dimethylated lysine 79 of histone H3 [25].”
BackgroundGranata, M., Lazzaro, F., Novarina, D., Panigada, D., Puddu, F., Abreu, C. M. C., Kumar, R., Grenon, M., Lowndes, N. F., Plevani, P., et al. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001047 · Cited by 71
“However, as expected, Rad9 chromatin recruitment is defective in dot1 D and H2A-S129A mutant cells, as binding of Rad9 is dependent upon H3-K79me and c H2A, via its Tudor and BRCT domains respectively [22,34,60].”
Lee, J., & Dunphy, W. G. (2010) · Molecular Biology of the Cell · doi:10.1091/mbc.e09-11-0958 · Cited by 74
“Several BRCA1 carboxy-terminal (BRCT) domain-containing proteins such as 53BP1 and Mdc1 recognize DSBs by interacting with chromatinbound proteins (Stewart et al., 2003; Huyen et al., 2004).”
ATM-mediated KDM2A phosphorylation is required for the DNA damage repair
Cao, L.-L., Wei, F., Du, Y., Song, B., Wang, D., Shen, C., Lu, X., Cao, Z., Yang, Q., Gao, Y., et al. (2015) · Oncogene · doi:10.1038/onc.2015.81 · Cited by 72
Cell Biology of Mitotic RecombinationPreprint
Lisby, M., & Rothstein, R. J. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016535 · Cited by 70
“2005) and 53BP1 binds to H3K79 (Huyen et al. 2004) and H4-K20 (Botuyan et al.”
BackgroundGao, X., Zhao, X., Zhu, Y., He, J., Shao, J., Su, C., Zhang, Y., Zhang, W., Saarikettu, J., Silvennoinen, O., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.311852 · Cited by 69
“For instance, the tudor domain of 53BP1 (51) and JMJD2A (52) can bindmethylated histone tails, but not the tudor domain ofDrosophilaTudor-SN protein (47).”
BackgroundDOT1L modulates the senescence-associated secretory phenotype through epigenetic regulation of IL1A
Leon, K. E., Buj, R., Lesko, E., Dahl, E. S., Chen, C.-W., Tangudu, N. K., Imamura-Kawasawa, Y., Kossenkov, A. V., Hobbs, R. P., & Aird, K. M. (2021) · Journal of Cell Biology · doi:10.1083/jcb.202008101 · Cited by 70
“DOT1L is also a regulator of DDR, and H3K79 methylation promotes 53BP1 binding to sites of DNA doublestrand breaks (FitzGerald et al., 2011; Huyen et al., 2004).”
Structure and Function of Histone H2AX
Pinto, D. M. S., & Flaus, A. (2009) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-90-481-3471-7_4 · Cited by 73
“The Rad9 Tudor domain binds H3 K79me (Grenon et al., 2007; Huyen et al., 2004 ) whereas Crb2 and 53BP1 Tudor domains bind H4 K20me2 (Sanders et al., 2004; Botuyan et al., 2006).”
BackgroundChromatin dynamics in DNA double-strand break repair
Shi, L., & Oberdoerffer, P. (2012) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2012.01.002 · Cited by 72
“A similar role for 53BP1 recruitment has been reported for methylation of H3K79 by the methyltransferase DOT1L [51] and recruitment to both H3K79me2 and H4K20me2 was shown to require the methyllysine binding tandem tudor domain of 53BP1 [48, 49].”
BackgroundAntigenic Variation in Trypanosoma brucei: Joining the DOTs
Stockdale, C., Swiderski, M. R., Barry, J. D., & McCulloch, R. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060185 · Cited by 67
Baldock, R. A., Day, M. W., Wilkinson, O. J., Cloney, R., Jeggo, P. A., Oliver, A. W., Watts, F. Z., & Pearl, L. H. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.10.074 · Cited by 74
“A 53BP1 construct with a Tudor domain mutation (Y1502L) that abolishes recruitment to DNA damage (Huyen et al., 2004; Botuyan et al., 2006) eliminated 53BP1 foci and did not restore focal concentration of either NBS1 or pATM.”
BackgroundGame, J. C., Williamson, M. S., Spicakova, T., & Brown, J. M. (2006) · Genetics · doi:10.1534/genetics.106.057794 · Cited by 67
“…ortholog of Saccharomyces RAD9) associates through its Tudor domain with methylated H3 K79, and it has been proposed that when DSBs occur, the preplaced methyl groups on this residue in the core of H3 become exposed near the DSBs, serving as a signal to bring Rad9p to the site (Huyen et al. 2004).”
BackgroundInfluentialHistone Ubiquitylation and the Regulation of Transcription
Osley, M. A., Fleming, A. B., & Kao, C.-F. (2006) · Results and problems in cell differentiation · doi:10.1007/400_006 · Cited by 66
Teijido, Ó., & Cacabelos, R. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19103199 · Cited by 69
“Histone methylation has also been associated with DNA repair [1,55,101,126].”
BackgroundNatural History of the Eukaryotic Chromatin Protein Methylation System
Aravind, L., Abhiman, S., & Iyer, L. M. (2011) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-387685-0.00004-4 · Cited by 65
Hoskins, E. E., Morris, T. A., Higginbotham, J. M., Spardy, N. A., Cha, E., Kelly, P. N., Williams, D., Wikenheiser‐Brokamp, K. A., Duensing, S. M., & Wells, S. I. (2008) · Oncogene · doi:10.1038/onc.2008.416 · Cited by 65
“53BP1 is a component of the DNA damage response and sensor of DNA double-strand breaks (Huyen et al., 2004).”
BackgroundEliezer, Y., Argaman, L., Rhie, A., Doherty, A. J., & Goldberg, M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m807375200 · Cited by 69
Di-methyl H4 Lysine 20 Targets the Checkpoint Protein Crb2 to Sites of DNA Damage
Greeson, N. T., Sengupta, R., Arida, A. R., Jenuwein, T., & Sanders, S. L. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m806857200 · Cited by 65
Chemical and biochemical approaches in the study of histone methylation and demethylation
Li, K. K., Luo, C., Wang, D., Jiang, H., & Zheng, Y. G. (2010) · Medicinal Research Reviews · doi:10.1002/mrr.20228 · Cited by 73
Zhao, Q., Qin, L., Jiang, F., Wu, B., Yue, W., Xu, F., Rong, Z., Yuan, H., Xie, X., Gao, Y., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m604029200 · Cited by 65
Histone modifications and the DNA double-strand break response
Van, H. T., & Santos, M. A. (2018) · Cell Cycle · doi:10.1080/15384101.2018.1542899 · Cited by 64
“X is required for the retention of 53BP1 at DSB sites [55].”
Lin, Y.-H., Kakadia, P. M., Chen, Y., Li, Y.-Q., Deshpande, A. J., Buske, C., Zhang, K.-L., Zhang, Y., Xu, G.-L., & Bohlander, S. K. (2009) · Blood · doi:10.1182/blood-2009-03-209395 · Cited by 64
Linking Cancer Metabolism to DNA Repair and Accelerated Senescence
Efimova, E. V., Takahashi, S., Shamsi, N. A., Wu, D., Labay, E., Ulanovskaya, O. A., Weichselbaum, R. R., Kozmin, S. A., & Kron, S. J. (2015) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-15-0263 · Cited by 65
“We have exploited GFP fused to the 53BP1 minimal IRIF binding domain (IBD), which consists of a nuclear localization domain, dimerization domain, paired Tudor domains and an ubiquitination-dependent recruitment (UDR) motif (21-23), as a live-cell reporter for DNA double strand break formation and repair in MCF7 human…”
Conde, F., Refolio, E., Cordón-Preciado, V., Cortés‐Ledesma, F., Aragón, L., Aguilera, A., & San-Segundo, P. A. (2009) · Genetics · doi:10.1534/genetics.109.101899 · Cited by 64
Antecedent chromatin organization determines cGAS recruitment to ruptured micronuclei
MacDonald, K. M., Nicholson-Puthenveedu, S., Tageldein, M. M., Khasnis, S., Arrowsmith, C. H., & Harding, S. M. (2023) · Nature Communications · doi:10.1038/s41467-023-36195-8 · Cited by 66
Burrage, J., Termanis, A., Geissner, A., Myant, K., Gordon, K., & Stancheva, I. (2012) · Journal of Cell Science · doi:10.1242/jcs.111252 · Cited by 70
“LSH-deficient MEFs display normal activation of DNA damage signalling In mammalian cells, IR-induced DSBs lead to activation of a DNA damage response (DDR) signalling which promotes the recruitment of mediator and repair proteins to the sites of DNA damage and simultaneously orchestrates cell cycle arrest while the br…”
BackgroundInfluentialChromatin dynamics during repair of chromosomal DNA double-strand breaks
Sinha, M., & Peterson, C. L. (2009) · Epigenomics · doi:10.2217/epi.09.22 · Cited by 63
Vidi, P., Liu, J., Salles, D. C., Jayaraman, S., Dorfman, G., Gray, M., Abad, P. C., Moghe, P. V., Irudayaraj, J., Wiesmüller, L., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku296 · Cited by 65
“Expression vectors for GFP-53BP1 (53BP1’s tudor domain fused to GFP; (25)), GFP-CtIP (26), GFP-NuMA (27), GFP- and RFPPCNA (28), SMRAD51 (29), and SNF2h1–643-GFP and GFP-SNF2h644–1053 (6) have been described previously.”
MLL-fusion-driven leukemia requires SETD2 to safeguard genomic integrity
Skucha, A., Ebner, J., Schmoellerl, J., Roth, M., Eder, T., César‐Razquin, A., Stukalov, A., Vittori, S., Muhar, M., Lu, B., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04329-y · Cited by 66
Erratum: ATM-mediated KDM2A phosphorylation is required for the DNA damage repair
Cao, L.-L., Wei, F., Du, Y., Song, B., Wang, D., Shen, C., Lu, X., Cao, Z., Yang, Q., Gao, Y., et al. (2016) · Oncogene · doi:10.1038/onc.2015.311 · Cited by 63
Chromatin perturbations during the DNA damage response in higher eukaryotes
Bakkenist, C. J., & Kastan, M. B. (2015) · DNA repair · doi:10.1016/j.dnarep.2015.09.002 · Cited by 64
“53BP1 binds H3K79me and chromatin decondensation has been implicated directly in the recruitment of 53BP1 to chromatin fiber on either side of the DSB [51].”
Systems-wide proteomic characterization of combinatorial post-translational modification patterns
Young, N. L., Plazas-Mayorca, M. D., & Garcia, B. A. (2010) · Expert Review of Proteomics · doi:10.1586/epr.09.100 · Cited by 62
Histone methylation in DNA repair and clinical practice: new findings during the past 5-years
Wei, S., Li, C., Yin, Z., Wen, J., Meng, H., Xue, L., & Wang, J. (2018) · Journal of Cancer · doi:10.7150/jca.23427 · Cited by 67
“So far, it has been found that the methylated H3K79, as a docking site, can recruit 53BP1 to drive NHEJ repair in G1/G2 phase in human cells when H4K20me2 levels are low [2, 34].”
BackgroundHistone Methyltransferases as Therapeutic Targets for Kidney Diseases
Yu, C., & Zhuang, S. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01393 · Cited by 62
“…mammalian development, cell cycle progression, cardiomyocyte differentiation, postembryonic development, somatic reprogramming, DNA damage response, and tumorigenesis (Huyen et al., 2004; Janzen et al., 2006; Jones et al., 2008; Wakeman et al., 2012; Wen et al., 2015; Cattaneo et al., 2016).”
BackgroundThe Role of Activation‐Induced Deaminase in Antibody Diversification and Chromosome Translocations
Ramiro, A. R., Reina‐San‐Martin, B., McBride, K. M., Janković, M., Barreto, V. M., Nussenzweig, A., & Nussenzweig, M. C. (2007) · Advances in immunology · doi:10.1016/s0065-2776(06)94003-6 · Cited by 64
Kilkenny, M. L., Doré, A. S., Roe, S. M., Nestoras, K., Ho, J. C.-Y., Watts, F. Z., & Pearl, L. H. (2008) · Genes & Development · doi:10.1101/gad.472808 · Cited by 62
“Toward the C terminus, all three possess a Tudor domain, which in the case of 53BP1 and Crb2 has been shown to interact with methylated lysine residues in histone H3 or H4 (Huyen et al. 2004; Sanders et al. 2004).”
BackgroundMigliori, V., Phalke, S., Bezzi, M., & Guccione, E. (2010) · Epigenomics · doi:10.2217/epi.09.39 · Cited by 63
Ontoso, D., Acosta, I., van Leeuwen, F., Freire, R., & San-Segundo, P. A. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003262 · Cited by 61
“, H3K79me, H4K20me) supporting the recruitment of DNA damage checkpoint adaptors to activate the checkpoint [44,45].”
BackgroundEpigenetic Information in Chromatin: the Code of Entry for DNA Repair
Loizou, J. I., Murr, R., Finkbeiner, M. G., Sawan, C., Wang, Z., & Herceg, Z. (2006) · Cell Cycle · doi:10.4161/cc.5.7.2616 · Cited by 67
Eberlein, U., Peper, M., Fernández, M., Laßmann, M., & Scherthan, H. (2015) · PLoS ONE · doi:10.1371/journal.pone.0123174 · Cited by 61
“In addition, DSBs also recruit the damage sensor 53BP1 to the chromatin domain surrounding a DSB [7–11] where it co-localizes with γ-H2AX [7,9,12].”
Huang, Z., Huang, Q., Ji, L., Wang, Y., Qi, X., Liu, L., Liu, Z., & Lu, L. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2016.09.023 · Cited by 62
“[67] Huyen Y, Zgheib O, Ditullio RA, Jr.”
BackgroundLi, T., Liu, Q., Garza, N., Kornblau, S. M., & Jin, V. X. (2018) · Genome Medicine · doi:10.1186/s13073-018-0538-1 · Cited by 63
Multiple cellular mechanisms prevent chromosomal rearrangements involving repetitive DNA
George, C. M., & Alani, E. (2012) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2012.675644 · Cited by 64
“Regulation of resection through both Rad9 and Sae2 are functions conserved in the mammalian homologs 53BP1 and CtIP (Huyen et al., 2004; Huertas and Jackson, 2009).”
BackgroundChernikova, S. B., Dorth, J. A., Razorenova, O. V., Game, J. C., & Brown, J. M. (2010) · Radiation Research · doi:10.1667/rr2184.1 · Cited by 60
“Separate evidence supporting the roles of each of H3K79me2 and H4K20me2 is strong (31, 32), so it seems that there is a role for both those modifications in radiation response in mammalian cells, with one of the two modifications probably being more important for a specific situation depending on the cell cycle stage…”
InfluentialHistone methyltransferases: regulation of transcription and contribution to human disease
Nimura, K., Ura, K., & Kaneda, Y. (2010) · Journal of Molecular Medicine · doi:10.1007/s00109-010-0668-4 · Cited by 61
“H3K79 targets 53BP1 that recognizes H3K79 and H4K20 di-methylation by a tandem tudor domain to DNA double-strand breaks [43, 44].”
BackgroundCurrent Perspectives on Histone Demethylases
Tian, X., & Fang, J. (2007) · Acta Biochimica et Biophysica Sinica · doi:10.1111/j.1745-7270.2007.00272.x · Cited by 61
“It was also suggested that the Tudor domain of the double-stranded break-sensing protein, 53BP1, can bind to H3K79me2 [68].”
BackgroundDNA damage in blood lymphocytes in patients after 177Lu peptide receptor radionuclide therapy
Eberlein, U., Nowak, C., Bluemel, C., Buck, A. K., Werner, R. A., Scherthan, H., & Laßmann, M. (2015) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-015-3083-9 · Cited by 59
DNA Damage in Peripheral Blood Lymphocytes of Thyroid Cancer Patients After Radioiodine Therapy
Eberlein, U., Scherthan, H., Bluemel, C., Peper, M., Lapa, C., Buck, A. K., Port, M., & Laßmann, M. (2015) · Journal of Nuclear Medicine · doi:10.2967/jnumed.115.164814 · Cited by 59
Tanaka, T., Kurose, A., Huang, X., Dai, W. H., & Darżynkiewicz, Z. (2006) · Cell Proliferation · doi:10.1111/j.1365-2184.2006.00364.x · Cited by 58
Tripathi, V., Nagarjuna, T., & Sengupta, S. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200610051 · Cited by 59
“Methylated lysine residues in the kinetochore binding domain modulate the accessibility of 53BP1 to the chromatin (Huyen et al., 2004; Botuyan et al., 2006).”
BackgroundExome sequencing reveals three novel candidate predisposition genes for diffuse gastric cancer
Donner, I., Kiviluoto, T. A., Ristimaki, A. P., Aaltonen, L. A., & Vahteristo, P. (2015) · Familial Cancer · doi:10.1007/s10689-015-9778-z · Cited by 60
DNA damage responses in skin biology—Implications in tumor prevention and aging acceleration
Nakanishi, M., Niida, H., Murakami, H., & Shimada, M. (2009) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2009.09.001 · Cited by 59
“For example, methylation of histone H3 at K79 by Dot1L is indispensable for recruitment of 53BP1 at damage sites [14].”
BackgroundDucroux, A., Benhenda, S., Rivière, L., Semmes, O. J., Benkirane, M., & Neuveut, C. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1004343 · Cited by 58
“For example, it has been shown that H3K79me2 mediates the recruitment of 53BP1 to DNA doublestrand breaks and methylation of 53BP1 or Mre11 modulates both their activities and their recruitment to DNA damage sites [50,51,52].”
BackgroundDual role of CDKs in DNA repair: To be, or not to be
Yata, K., & Esashi, F. (2008) · DNA repair · doi:10.1016/j.dnarep.2008.09.002 · Cited by 62
Antigen receptor diversification and chromosome translocations
Janković, M., Nussenzweig, A., & Nussenzweig, M. C. (2007) · Nature Immunology · doi:10.1038/ni1498 · Cited by 61
“This protein is initially targeted to DSBs through interactions with methylated lysine residues on histones that become exposed after genotoxic stres”
BackgroundATM Activation by Ionizing Radiation Requires BRCA1-associated BAAT1
Aglipay, J. A., Martin, S. A., Tawara, H., Lee, S. W., & Ouchi, T. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m510332200 · Cited by 59
Chaudhuri, S., Wyrick, J. J., & Smerdon, M. J. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp003 · Cited by 58
“Unlike histone acetylation, histone methylation does not appear to be induced by DNA damage (22).”
BackgroundReading chromatin signatures after DNA double-strand breaks
Wilson, M. D., & Durocher, D. (2017) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0280 · Cited by 60
Activation and regulation of H2B-Ubiquitin-dependent histone methyltransferases
Worden, E. J., & Wolberger, C. (2019) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2019.05.009 · Cited by 58
Epigenomics and the Regulation of Aging
Boyd-Kirkup, J. D., Green, C. D., Wu, G., Wang, D., & Han, J. J. (2013) · Epigenomics · doi:10.2217/epi.13.5 · Cited by 57
The histone methyltransferase DOT1L: regulatory functions and a cancer therapy target.
Wong, M., Polly, P., & Liu, T. (2015) · Europe PMC (PubMed Central) · Cited by 57
Targeting Epigenetic Mechanisms: Potential of Natural Products in Cancer Chemoprevention
Hauser, A., & Jung, M. (2008) · Planta Medica · doi:10.1055/s-2008-1081347 · Cited by 56
Discordance between phosphorylation and recruitment of 53BP1 in response to DNA double-strand breaks
Harding, S. M., & Bristow, R. G. (2012) · Cell Cycle · doi:10.4161/cc.19824 · Cited by 54
“These chromatin modifications expose constitutively dimethylated K79 and K20 residues on histones H3 and H4, respectively, to concentrate 53BP1 at the DSB break site.(8,9) During the DNA damage response (DDR), chromatin modifications contribute to localization of 53Bp1 to sites of DNA double-strand breaks (DSBs).”
BackgroundStructure of the Chromo Barrel Domain from the MOF Acetyltransferase
Nielsen, P. R., Nietlispach, D., Buscaino, A., Warner, R. J., Akhtar, A., Murzin, A. G., Murzina, N. V., & Laue, E. D. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501347200 · Cited by 56
Characterization of the DOT1L Network: Implications of Diverse Roles for DOT1L
Park, G., Gong, Z., Chen, J., & Kim, J. (2010) · The Protein Journal · doi:10.1007/s10930-010-9242-8 · Cited by 56
Human Mismatch Repair Protein MSH6 Contains a PWWP Domain That Targets Double Stranded DNA
Laguri, C., Duband‐Goulet, I., Friedrich, N., Axt, M., Belin, P., Callebaut, I., Gilquin, B., Zinn‐Justin, S., & Couprie, J. (2008) · Biochemistry · doi:10.1021/bi7024639 · Cited by 56
γH2AX Assay as DNA Damage Biomarker for Human Population Studies: Defining Experimental Conditions
Sánchez-Flores, M., Pásaro, E., Bonassi, S., Laffón, B., & Valdiglesias, V. (2015) · Toxicological Sciences · doi:10.1093/toxsci/kfv011 · Cited by 56
“This observation agrees with other previous studies in which resting cells resulted less sensitive to the induction of DNA damage than proliferating cells (Huyen et al., 2004; Mohrin et al., 2010; Tian et al., 2011).”
ResultTelomeres, histone code, and DNA damage response
Misri, S., Pandita, S., Kumar, R., & Pandita, T. K. (2008) · Cytogenetic and Genome Research · doi:10.1159/000167816 · Cited by 54
Dynamics of Chromatin during the Repair of DNA Double-Strand Breaks
Downs, J. A., & Côté, J. (2005) · Cell Cycle · doi:10.4161/cc.4.10.2108 · Cited by 55
Quinn, A. M., Bedford, M. T., Espejo, A. B., Spannhoff, A., Austin, C. P., Oppermann, U. C. T., & Simeonov, A. M. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp899 · Cited by 56
Pagano, A., Araújo, S. D. S., Macovei, A., Leonetti, P., & Balestrazzi, A. (2017) · Frontiers in Plant Science · doi:10.3389/fpls.2017.01972 · Cited by 54
“It is also possible that DSBs-induced DDR networks result in chromatin alterations, such as the presentation of methylated lysine 79 of histone H3, thus facilitating the binding of TRRAPcontaining HAT complexes at the damaged site (Huyen et al., 2004).”
BackgroundActivation of DNA damage signaling
Ljungman, M. E. (2005) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2005.02.014 · Cited by 54
Chromatin structure in double strand break repair
Gospodinov, A. G., & Herceg, Z. (2013) · DNA repair · doi:10.1016/j.dnarep.2013.07.006 · Cited by 56
Protein methylation and DNA repair
Lake, A., & Bedford, M. T. (2007) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2006.09.010 · Cited by 54
Structural Insight into p53 Recognition by the 53BP1 Tandem Tudor Domain
Roy, S., Musselman, C. A., Kachirskaia, I., Hayashi, R., Glass, K. C., Nix, J. C., Gozani, O., Appella, E., & Kutateladze, T. G. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.03.024 · Cited by 53
Chen, Y., & Zhu, W. (2016) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmw050 · Cited by 57
Leopardi, P. (2006) · Mutagenesis · doi:10.1093/mutage/gel031 · Cited by 53
“The impaired methylation of critical targets, such as chromatin-associated proteins involved in repair of DNA double strand breaks (44), could explain the lower efficiency in the processing of radiation induced damage in MTHFR cells.”
BackgroundOn the road with WRAP53β: guardian of Cajal bodies and genome integrity
Henriksson, S., & Farnebo, M. (2015) · Frontiers in Genetics · doi:10.3389/fgene.2015.00091 · Cited by 57
“Interestingly, SMN interacts with methylated H3K79 in chromatin via its Tudor domain, a site known to target 53BP1 to DNA double-strand breaks (Huyen et al., 2004; Sabra et al., 2013).”
BackgroundH2AX: tailoring histone H2A for chromatin-dependent genomic integrity
Li, A., Eirin-Lopez, J. M., & Ausió, J. (2005) · Biochemistry and Cell Biology · doi:10.1139/o05-114 · Cited by 55
“Programmed DSB formation also occurs in germ cells during meiotic recombination ( Hunter et al. 2001; Mahadevaiah et al. 2001), when DSBs are repaired by HR. Indeed, phosphorylated H2AX has been shown to be temporally and spatially linked to Spo11, a topoisomerase II-like protein responsible for DSB formation during m…”
BackgroundSadeghi, F., Asgari, M., Matloubi, M., Ranjbar, M., Yousefi, N. K., Azari, T., & Zaki‐Dizaji, M. (2020) · Biological Procedures Online · doi:10.1186/s12575-020-00133-5 · Cited by 55
“site and mediates the recruitment of BRCA1 by methylated H3 Lys 79 and signals chromatin/DNA damage [161].”
BackgroundTargeting the epigenetic machinery of cancer cells
Montenegro, M. F., Sánchez‐del‐Campo, L., Fernández-Pérez, M. P., Sáez‐Ayala, M., Cabezas‐Herrera, J., & Rodríguez‐López, J. N. (2014) · Oncogene · doi:10.1038/onc.2013.605 · Cited by 51
Chromatin Structure Following UV-Induced DNA Damage—Repair or Death?
Farrell, A. W., Halliday, G. M., & Lyons, J. G. (2011) · International Journal of Molecular Sciences · doi:10.3390/ijms12118063 · Cited by 51
Chromatin Response to DNA Double-Strand Break Damage
Bao, Y. (2011) · Epigenomics · doi:10.2217/epi.11.14 · Cited by 51
Bayona‐Feliú, A., Herrera‐Moyano, E., Badra-Fajardo, N., Galván‐Femenía, I., Soler-Oliva, M. E., & Aguilera, A. (2023) · Nature Communications · doi:10.1038/s41467-023-42653-0 · Cited by 51
“Indeed, this histone PTM is closely linked to the DDR, as it is required for Rad9 recruitment in S. cerevisiae 59 – 61 and for 53BP1 recruitment in mammalian cells, being particularly abundant at transcribed genes 59,62,63 .”
Effects of Zinc and DHA on the Epigenetic Regulation of Human Neuronal Cells
Sadli, N., Ackland, M. L., Mel, D. D., Sinclair, A. J., & Suphioglu, C. (2012) · Cellular Physiology and Biochemistry · doi:10.1159/000337590 · Cited by 49
Histone Methyltransferase DOT1L as a Promising Epigenetic Target for Treatment of Solid Tumors
Alexandrova, E., Salvati, A., Pecoraro, G., Lamberti, J., Melone, V., Sellitto, A., Rizzo, F. M., Giurato, G., Tarallo, R., Nassa, G., et al. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.864612 · Cited by 53
“, 1998), DNA repair (Huyen et al., 2004), transcription elongation (Mueller et al.”
BackgroundHistone Post-Translational Modifications in DNA Damage Response
Méndez-Acuña, L., Tomaso, M. V. D., Palitti, F., & Martínez‐López, W. (2010) · Cytogenetic and Genome Research · doi:10.1159/000296275 · Cited by 49
“This lysine would be constitutively methylated and changes in chromatin conformation after DSB induction would expose it, leading to 53BP1 recruitment [Huyen et al., 2004].”
BackgroundKu70 and non-homologous end joining protect testicular cells from DNA damage
Ahmed, E. A., Sfeir, A. J., Takai, H., & Scherthan, H. (2013) · Journal of Cell Science · doi:10.1242/jcs.122788 · Cited by 48
BRCT domains: A little more than kin, and less than kind
Gerloff, D. L., Woods, N. T., Farago, A. A., & Monteiro, Á. N. A. (2012) · FEBS Letters · doi:10.1016/j.febslet.2012.05.005 · Cited by 51
Bigot, N., Mouche, A., Preti, M., Loisel, S., Renoud, M.-L., Guével, R. L., Sensebé, L., Tarte, K., & Pedeux, R. (2015) · Stem Cells · doi:10.1002/stem.2195 · Cited by 49
Puddu, F., Piergiovanni, G., Plevani, P., & Muzi-Falconi, M. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002022 · Cited by 48
“complex and Dpb11 [16,17,18,19,20].”
Wallace, N. A., Robinson, K. L., Howie, H. L., & Galloway, D. A. (2015) · PLoS Pathogens · doi:10.1371/journal.ppat.1004687 · Cited by 53
Roidl, D., Hellbach, N., Bovio, P. P., Villarreal, A., Heidrich, S., Nestel, S., Grüning, B. A., Bönisch, U., & Vogel, T. (2015) · Stem Cells · doi:10.1002/stem.2187 · Cited by 48
Zhang, A., Peng, B., Huang, P. C., Chen, J., & Gong, Z. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.777474 · Cited by 48
“At sites of DNA breaks, 53BP1 not only associates with methylated and ubiquitinated histones, as reported previously (8, 21, 22), but also binds to other chromatin proteins, which may retain 53BP1 at damage sites and function with 53BP1 to carry out DNA repair and cellular response to PARP inhibitors (Fig.”
BackgroundLoss of Histone H3 Methylation at Lysine 4 Triggers Apoptosis in Saccharomyces cerevisiae
Walter, D., Matter, A., & Fahrenkrog, B. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004095 · Cited by 50
“Moreover, H3K79 methylation is critical for proper DNA damage response (DDR) [32,33], as it is prerequisite for Rad9p (53BP1) recruitment [34].”
BackgroundIwasaki, W., Tachiwana, H., Kawaguchi, K., Shibata, T., Kagawa, W., & Kurumizaka, H. (2011) · Biochemistry · doi:10.1021/bi201021h · Cited by 47
DNA double-strand break repair: a tale of pathway choices
Li, J., & Xu, X. (2016) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmw045 · Cited by 53
“The Tudor domain of 53BP1 binds to H4K20me and H4K20me2, which is essential for the recruitment of 53BP1 to DSB foci [44].”
BackgroundH3K9me3 and H4K20me3 represent the epigenetic landscape for 53BP1 binding to DNA lesions
Kovaříková, A. S., Legartová, S., Krejčí, J., & Bártová, E. (2018) · Aging · doi:10.18632/aging.101572 · Cited by 47
“Moreover, Simonetta et al. [20] showed that MAD2L2 (a homolog of yeast mitotic arrest-deficient protein, Mad2) accumulates at DSBs in DNA, which are associated with H4K20 di-methylated histones.”
BackgroundInfluentialCBX8 exhibits oncogenic properties and serves as a prognostic factor in hepatocellular carcinoma
Tang, B., Tian, Y., Liao, Y., Li, Z., Yu, S., Su, H., Zhong, F., Yuan, G., Wang, Y., Yu, H., et al. (2019) · Cell Death and Disease · doi:10.1038/s41419-018-1288-0 · Cited by 47
Chromatin at the intersection of viral infection and DNA damage
Lilley, C. E., Chaurushiya, M. S., & Weitzman, M. D. (2009) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2009.06.007 · Cited by 49
“Poorly understood chromatin remodeling events then ensue, culminating in the exposure of methylated histone H4K20, the target of cellular SET domain methyltransferases and the binding site for the DNA damage protein 53BP1 [10,11].”
Background
Metadata
- Authors
- Huyen, Y., Zgheib, O., DiTullio Jr, R. A., Gorgoulis, V. G., Zacharatos, P., Petty, T. J., Sheston, E. A., Mellert, H. S., Stavridi, E. S., & Halazonetis, T. D.
- Affiliations
- The Wistar Institute (US)
- Corresponding author
- Halazonetis, Thanos D.
- Venue
- Nature
- Published
- 2004-11
- Volume
- 432
- Issue
- 7015
- Pages
- 406-411
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2038451572
- Cited by
- 884
- References
- 30
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 14 · 2023: 20 · 2022: 20 · 2021: 34 · 2020: 27 · 2019: 37 · 2018: 32 · 2017: 27 · 2016: 37 · 2015: 44 · 2014: 34 · 2013: 51 · 2012: 57
- FWCI
- 22.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- University of Pennsylvania
- National Cancer Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- 53BP1, histone H3 lysine 79 methylation, DNA double-strand breaks, DNA damage checkpoint, Tudor domain, DOT1L, chromatin structure, DNA damage recognition, Rad9, protein-DNA interactions
- MeSH terms
- Tumor Suppressor p53-Binding Protein 1, Amino Acid Sequence, Binding Sites, Chromatin, Cross-Linking Reagents, DNA, DNA Damage, Histones, Humans, Lysine, Methylation, Methyltransferases, Models, Molecular, Molecular Sequence Data, Phosphoproteins, Protein Binding, Histone-Lysine N-Methyltransferase, Conserved Sequence, Protein Structure, Tertiary, Cell Line, Tumor, Intracellular Signaling Peptides and Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
