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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.
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“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]
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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
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Zhang, K., & Jagannath, C. (2025) · Epigenetics & Chromatin · doi:10.1186/s13072-025-00575-9 · Cited by 137
“Additionally, methylation of histone H3 lysine 36 (H3K36me) plays a critical role in the regulation of alternative splicing of RNA and RNA elongation [39, 40], and methylation of histone H3 lysine 79 (H3K79me) is involved in the DNA damage response [41].”
An Oligomerized 53BP1 Tudor Domain Suffices for Recognition of DNA Double-Strand Breaks
Zgheib, O., Pataky, K. A., Brügger, J., & Halazonetis, T. D. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01011-08 · Cited by 124
Self-citationEpigenetic regulation in African trypanosomes: a new kid on the block
Figueiredo, L. M., Cross, G., & Janzen, C. J. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2149 · Cited by 119
“Furthermore, DOT1 is involved in meiotic checkpoint control and the DNA damage respons”
BackgroundZhang, D., Yoon, H., & Wong, J. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.15.6404-6414.2005 · Cited by 118
“In addition, a recent report showed that the tandem Tudor domain of mammalian checkpoint protein 53BP1 binds specifically to lysine 79-methylated histone H3 and plays a role in double-strand DNA break repair (19).”
BackgroundBártková, J., Hořejší, Z., Sehested, M., Nesland, J. M., Meyts, E. R., Skakkebæk, N. E., Stucki, M., Jackson, S. P., Lukáš, J., & Bártek, J. (2007) · Oncogene · doi:10.1038/sj.onc.1210553 · Cited by 117
“Whereas claspin and TopBP1 are involved in ATR/Chk1-mediated signalling (Kumagai and Dunphy, 2000; Kumagai et al., 2006; Liu et al., 2006), the remaining mediator proteins contribute to efficient responses to DNA double strand breaks (DSBs) mediated by ATM (DiTullio et al., 2002; Goldberg et al., 2003; Mochan et al.,…”
BackgroundInfluentialFerrari, M., Dibitetto, D., Gregorio, G. D., Eapen, V. V., Rawal, C. C., Lazzaro, F., Tsabar, M., Marini, F., Haber, J. E., & Pellicioli, A. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1004928 · Cited by 112
“and the histone H3 methylated at the K79 by Dot1 [20,21,22].”
BackgroundInfluentialNakamura, K. M., Sakai, W., Kawamoto, T., Bree, R. T., Lowndes, N. F., Takeda, S., & Taniguchi, Y. (2006) · DNA repair · doi:10.1016/j.dnarep.2006.03.008 · Cited by 111
He, M., Xu, Y., Chen, J., Luo, Y., Lv, Y., Su, J., Kershaw, M. J., Li, W., Wang, J., Yin, J., et al. (2018) · Autophagy · doi:10.1080/15548627.2018.1458171 · Cited by 116
“GST-affinity isolation assay was performed following the method as described previously [75].”
MethodIdentification of Histone Demethylases in Saccharomyces cerevisiae
Tu, S., Bulloch, E. M. M., Yang, L., Ren, C., Huang, W.-C., Hsu, P., Chen, C., Liao, C.-L., Yu, H., Lo, W., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m609900200 · Cited by 116
Assembly of checkpoint and repair machineries at DNA damage sites
Huen, M. S. Y., & Chen, J. (2009) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2009.09.001 · Cited by 118
USP3 counteracts RNF168 via deubiquitinating H2A and γH2AX at lysine 13 and 15
Sharma, N., Zhu, Q., Wani, G., He, J., Wang, Q.-E., & Wani, A. A. (2013) · Cell Cycle · doi:10.4161/cc.26814 · Cited by 120
“com Cell Cycle 109 USP3 overexpression leads to an impaired recruitment of DNA damage repair factors Recent studies suggest that histone ubiquitination by E3 ligases such as RNF8 and RNF168 triggers and facilitates the accumulation of DNA repair factors BRCA1 and 53BP1 at DNA damage sites.(13-15,29,30) The assembly of…”
BackgroundLi, C.-L., Yang, W., Chen, Y. P., & Yuan, H. S. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn236 · Cited by 116
“The tudor domain, bearing a barrel-like fold, is a protein– protein interaction domain, usually interacting with methylated peptides, such as the ones identified in SMN (23), 53BP1 (24), SPF30 and TDRD (25).”
BackgroundWakeman, T. P., Wang, Q., Feng, J., & Wang, X. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.50 · Cited by 113
“Interestingly, similar to DOT1L, Bat3 is also known to function in embryonic development, cell division, and cell cycle checkpoint activation (Huyen et al , 2004; Mu et al , 2007).”
InfluentialThe cellular response to DNA damage: A focus on MDC1 and its interacting proteins
Coster, G., & Goldberg, M. (2010) · Nucleus · doi:10.4161/nucl.1.2.11176 · Cited by 115
Efimova, E. V., Mauceri, H. J., Golden, D. W., Labay, E., Bindokas, V. P., Darga, T. E., Chakraborty, C., Barreto-Andrade, J. C., Crawley, C. D., Sutton, H. G., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-4224 · Cited by 118
“Cell cultures and constructs GFP fused to the human 53BP1 IRIF binding domain (10) was cloned into the pLVX-Tight-Puro lentiviral vector (Clontech), transduced into the MCF7 Tet-On Advanced cell line (Clontech), and cultured in high-glucose DMEM (Invitrogen) with 10% Tet system-approved fetal bovine serum (Clontech).”
Structural and biochemical studies of the 5′→3′ exoribonuclease Xrn1
Chang, J. H., Xiang, S., Xiang, K., Manley, J. L., & Tong, L. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1984 · Cited by 113
H3K36me3, message from chromatin to DNA damage repair
Sun, Z., Zhang, Y., Jia, J., Fang, Y., Tang, Y., Wu, H., & Fang, D. (2020) · Cell & Bioscience · doi:10.1186/s13578-020-0374-z · Cited by 109
Chemical proteomics reveals a γH2AX-53BP1 interaction in the DNA damage response
Kleiner, R. E., Verma, P., Molloy, K. R., Chait, B. T., & Kapoor, T. M. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1908 · Cited by 112
Li, L., Ma, N., Zhou, H. W., Wang, Q., Zhang, H., Wang, P., Hou, H., Wen, H., & Gao, F. (2016) · International Journal of Nanomedicine · doi:10.2147/ijn.s107021 · Cited by 109
“This ZnO NP-induced hypermethylation of chromatin might control the accessibility of damaged regions of DNA to repair signaling proteins.(55,56) The ability of NPs to induce toxicity has been attributed to their increased surface reactivity.”
BackgroundDocking onto chromatin via the Saccharomyces cerevisiae Rad9 Tudor domain
Grenon, M., Costelloe, T., Jimeno, S., O'Shaughnessy, A. M., Fitzgerald, J., Zgheib, O., Degerth, L., & Lowndes, N. F. (2007) · Yeast · doi:10.1002/yea.1441 · Cited by 110
“…to histones prepared from non-irradiated and irradiated cells, thereby supporting the conclusion that in vivo DNA double-strand breaks lead to a change in chromatin structure that would expose the interacting residue, similar to the conclusion drawn from a 53BP1 binding study (Huyen et al., 2004).”
BackgroundMethodInfluentialSelf-citationHistone modifications in response to DNA damage
Altaf, M., Saksouk, N., & Côté, J. (2007) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2006.09.009 · Cited by 109
Integrating the DNA damage and protein stress responses during cancer development and treatment
Gorgoulis, V. G., Pefani, D., Pateras, I. S., & Trougakos, I. P. (2018) · The Journal of Pathology · doi:10.1002/path.5097 · Cited by 108
“In NHEJ, the DSB is sensed by the lupus Ku autoantigen protein p80 (Ku80)–lupus Ku autoantigen protein p70 (Ku70) heterodimer, which recruits and assembles the DNA–PK complex, which, in turn, processes the DNA ends and increases the recruitment of ligase IV/X-ray repair complementing defective repair in Chinese hamste…”
BackgroundInfluentialSelf-citationDNA double strand break repair pathway choice: a chromatin based decision?
Clouaire, T., & Legube, G. (2015) · Nucleus · doi:10.1080/19491034.2015.1010946 · Cited by 124
Yao, H., & Rahman, I. (2012) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00175.2012 · Cited by 109
Histone methyltransferase DOT1L coordinates AR and MYC stability in prostate cancer
Vatapalli, R. J., Sagar, V., Rodríguez, Y., Zhao, J. C., Unno, K., Pamarthy, S., Lysy, B., Anker, J. F., Han, H., Yoo, Y. A., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18013-7 · Cited by 111
Topoisomerase IIα controls the decatenation checkpoint
Luo, K., Yuan, J., Chen, J., & Lou, Z. (2008) · Nature Cell Biology · doi:10.1038/ncb1828 · Cited by 111
“It has been shown previously that methylation at histone H3 and H4 can recruit DNA damage factors 53BP1 to sites of DNA damag”
The γ‐H2A.X: Is it just a surrogate marker of double‐strand breaks or much more?
Ismail, I. H., & Hendzel, M. J. (2007) · Environmental and Molecular Mutagenesis · doi:10.1002/em.20358 · Cited by 114
“Alternatively, it is possible that a kinase other than ATM, ATR, and DNA-Pkcs may be responsible for the formation of these g-H2A.”
BackgroundInfluentialEpigenetic regulation of development by histone lysine methylation
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HP1 promotes tumor suppressor BRCA1 functions during the DNA damage response
Lee, Y.-H., Kuo, C., Stark, J. M., Shih, H., & Ann, D. K. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt231 · Cited by 116
The ubiquitin‐ and SUMO‐dependent signaling response to DNA double‐strand breaks
Bekker‐Jensen, S., & Mailand, N. (2011) · FEBS Letters · doi:10.1016/j.febslet.2011.05.056 · Cited by 115
“overall levels of these epigenetic marks do not seem to change significantly after genotoxic insults [58,62], it is not understood how”
BackgroundAbbosh, P. H., Montgomery, J. S., Starkey, J. A., Novotný, M. V., Zuhowski, E. G., Egorin, M. J., Moseman, A. P., Golas, A. A., Brannon, K. M., Balch, C., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3575 · Cited by 109
Keeping it in the family: diverse histone recognition by conserved structural folds
Yap, K. L., & Zhou, M. (2010) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2010.512001 · Cited by 111
“53BP1 TTD was also identified as a binding module for H3K79me2, and this interaction was reportedly necessary for targeting to DSBs (Huyen et al., 2004).”
BackgroundResponding to DNA double strand breaks in the nervous system
Lee, Y., & McKinnon, P. J. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.07.026 · Cited by 105
The upstreams and downstreams of H3K79 methylation by DOT1L
Vlaming, H., & van Leeuwen, F. (2016) · Chromosoma · doi:10.1007/s00412-015-0570-5 · Cited by 106
“2013) and the tandem Tudor domains of fragile Xmental retardation protein (FMRP) and 53BP1 (Huyen et al. 2004; Alpatov et al. 2014).”
BackgroundThe significance, development and progress of high-throughput combinatorial histone code analysis
Young, N. L., DiMaggio, P. A., & Garcia, B. A. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0475-7 · Cited by 103
“In an apparent trans-histone combinatorial code spanning three different histone modifications on three different histones, H4K20me2 and H3K79 methylations both appear to be involved in the relocation of 53BP1 to sites of DNA DSBs, and H2AX phosphorylation has been implicated in its retention [8, 41, 42 ].”
BackgroundBecker, J. R., Cuella-Martin, R., Barazas, M., Liu, R., Oliveira, C., Oliver, A. W., Bilham, K., Holt, A. B., Blackford, A. N., Heierhorst, J., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-07855-x · Cited by 105
MDC1: The art of keeping things in focus
Jungmichel, S., & Stucki, M. (2010) · Chromosoma · doi:10.1007/s00412-010-0266-9 · Cited by 104
“These domains may bind to methylated histone marks that are masked in unperturbed chromatin, but may become locally exposed in a ubiquitin-dependent manner in response to DNA damage (Botuyan et al. 2006; Huyen et al. 2004 ).”
BackgroundCurrent Topics in DNA Double-Strand Break Repair
Kobayashi, J., Iwabuchi, K., Miyagawa, K., Sonoda, E., Suzuki, K., Takata, M., & Tauchi, H. (2008) · Journal of Radiation Research · doi:10.1269/jrr.07130 · Cited by 102
Protein lysine methylation by seven-β-strand methyltransferases
Falnes, P. Ø., Jakobsson, M. E., Davydova, E., Ho, A. Y. Y., & Małecki, J. (2016) · Biochemical Journal · doi:10.1042/bcj20160117 · Cited by 100
Changes in H3K79 Methylation During Preimplantation Development in Mice
Ooga, M., Inoue, A., Kageyama, S., Akiyama, T., Nagata, M., & Aoki, F. (2007) · Biology of Reproduction · doi:10.1095/biolreprod.107.063453 · Cited by 105
“In fact, 53BP1, which plays a pivotal role in the DNA repair mechanism, binds to H3K79me2, and the decrease in the level of H3K79me2 by suppressing DOT1L, which catalyzes the methylation of H3K79, reduces the recruitment of 53BP1 to the sites of double-strand breaks and induces DNA damage checkpoint defects [60, 61].”
BackgroundLiu, Q., Ma, L., Jones, T., Palomero, L., Pujana, M. Á., Martinez‐Ruiz, H., Ha, P. K., Murnane, J. P., Cuartas, I., Seoane, J., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-1346 · Cited by 100
“In addition, failure of ATM kinase impairs DSB recognition, which is often assessed by analyzing H2AX, itself a substrate for ATM phosphorylation (53).”
BackgroundDNA double-strand breaks: Their production, recognition, and repair in eukaryotes
Ohnishi, T., Mori, E., & Takahashi, A. (2009) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/j.mrfmmm.2009.06.010 · Cited by 98
Shukla, A., Chaurasia, P., & Bhaumik, S. R. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-8605-1 · Cited by 98
What histone code for DNA repair?
Escargueil, A. E., Soares, D. G., Salvador, M. M., Larsen, A. K., & Henriques, J. A. P. (2008) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2008.01.004 · Cited by 101
Fu, H., Maunakea, A. K., Martin, M. M., Huang, L., Zhang, Y., Ryan, M., Kim, R., Lin, C. M., Zhao, K., & Aladjem, M. I. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003542 · Cited by 98
“of 53BP1 to DNA damage lesions [24].”
Spreading of mammalian DNA‐damage response factors studied by ChIP‐chip at damaged telomeres
Meier, A., Fiegler, H., Muñoz, P., Ellis, P., Rigler, D., Langford, C., Blasco, M. A., Carter, N., & Jackson, S. P. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601719 · Cited by 100
“…retention of 53BP1 in DNAdamage foci requires gH2AX and MDC1 (Celeste et al, 2002; Ward et al, 2003; Bekker-Jensen et al, 2005), it is clear that methylated lysine residues in histone proteins play a major role in 53BP1 recruitment to DNA-damage sites (Huyen et al, 2004; Botuyan et al, 2006).”
BackgroundKang, J., Kim, J., Kim, K., Park, J. W., Cho, H., Hahm, J. Y., Chae, Y., Kim, D., Kook, H. Y., Rhee, S., et al. (2018) · The FASEB Journal · doi:10.1096/fj.201800242r · Cited by 103
TopBP1 functions with 53BP1 in the G1 DNA damage checkpoint
Cescutti, R., Negrini, S., Kohzaki, M., & Halazonetis, T. D. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.238 · Cited by 97
“However, unlike TopBP1, 53BP1 localizes to sites of DNA DSBs (Schultz et al, 2000; Anderson et al, 2001; Rappold et al, 2001; Xia et al, 2001; Huyen et al, 2004).”
BackgroundMethodSelf-citationHong, Z., Jiang, J., Lan, L., Nakajima, S., Kanno, S.-I., Koseki, H., & Yasui, A. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn146 · Cited by 98
“It has been reported that the two tandem Tudor domains of 53BP1 binds to methylated lysine 79 of histone H3 in response to DNA damage (24,25).”
Background53BP1-mediated DNA double strand break repair: Insert bad pun here
Noon, A. T., & Goodarzi, A. A. (2011) · DNA repair · doi:10.1016/j.dnarep.2011.07.012 · Cited by 94
Grabarz, A., Barascu, A., Guirouilh‐Barbat, J., & López, B. S. (2012) · Europe PMC (PubMed Central) · Cited by 93
Preserving genome integrity and function: the DNA damage response and histone modifications
Kim, J. J., Lee, S. Y., & Miller, K. M. (2019) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2019.1620676 · Cited by 96
“53BP1 binds to chromatin surrounding a DSB lesion through its bivalent interactions with two histone PTMs, H4K20me2, and H2AK15ub (Huyen et al. 2004; Botuyan et al. 2006; Fradet-Turcotte et al. 2013).”
BackgroundHistone methylation and aging: Lessons learned from model systems
McCauley, B. S., & Dang, W. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.05.008 · Cited by 93
Franco, S., Alt, F. W., & Manis, J. P. (2006) · DNA repair · doi:10.1016/j.dnarep.2006.05.024 · Cited by 96
Ahmed, E. A., van der Vaart, A., Barten, A., Kal, H. B., Chen, J., Lou, Z., Minter‐Dykhouse, K., Bártková, J., Bártek, J., & de Boer, P. (2007) · DNA repair · doi:10.1016/j.dnarep.2007.02.011 · Cited by 95
A Glycine-Arginine Domain in Control of the Human MRE11 DNA Repair Protein
Déry, U., Coulombe, Y., Rodrigue, A., Stasiak, A., Richard, S., & Masson, J. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.02025-07 · Cited by 90
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BackgroundGenetic instability in cancer cells by impaired cell cycle checkpoints
Nakanishi, M., Shimada, M., & Niida, H. (2006) · Cancer Science · doi:10.1111/j.1349-7006.2006.00289.x · Cited by 93
53BP1 and p53 synergize to suppress genomic instability and lymphomagenesis
Morales, J. C., Franco, S., Murphy, M. M., Bassing, C. H., Mills, K. D., Adams, M. M., Walsh, N. C., Manis, J. P., Rassidakis, G. Z., Alt, F. W., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0511259103 · Cited by 92
Zgheib, O., Huyen, Y., DiTullio, R. A., Snyder, A. R., Venere, M., Stavridi, E. S., & Halazonetis, T. D. (2005) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2005.06.026 · Cited by 90
“Indeed, in vitro the tandem tudor domain of 53BP1 bound histone H3 [15].”
BackgroundSelf-citationA Structural Perspective on Readout of Epigenetic Histone and DNA Methylation MarksPreprint
Patel, D. J. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a018754 · Cited by 91
Javaheri, A., Wysocki, R., Jobin‐Robitaille, O., Altaf, M., Côté, J., & Kron, S. J. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0511192103 · Cited by 89
Bostelman, L. J., Keller, A. M., Albrecht, A. M., Arat, A., & Thompson, J. S. (2007) · DNA repair · doi:10.1016/j.dnarep.2006.12.010 · Cited by 85
RAP80 and RNF8, key players in the recruitment of repair proteins to DNA damage sites
Yan, J., & Jetten, A. M. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.04.046 · Cited by 90
BRCA1/BARD1 site-specific ubiquitylation of nucleosomal H2A is directed by BARD1
Witus, S. R., Burrell, A. L., Farrell, D. P., Kang, J., Wang, M., Hansen, J. M., Pravat, A., Tuttle, L. M., Stewart, M. D., Brzović, P. S., et al. (2021) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-00556-4 · Cited by 85
Role for 53BP1 Tudor Domain Recognition of p53 Dimethylated at Lysine 382 in DNA Damage Signaling
Kachirskaia, I., Shi, X., Yamaguchi, H., Tanoue, K., Wen, H., Wang, E. W., Appella, E., & Gozani, O. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m806020200 · Cited by 84
BRCA2 functions: from DNA repair to replication fork stabilization
Fradet‐Turcotte, A., Sitz, J., Grapton, D., & Orthwein, A. (2016) · Endocrine Related Cancer · doi:10.1530/erc-16-0297 · Cited by 91
Posttranslational modifications of human histone H3: An update
Xu, Y., Du, J.-Y., & Lau, A. T. Y. (2014) · PROTEOMICS · doi:10.1002/pmic.201300435 · Cited by 89
“Methylated H3K79 is also associated with DNA DSB responses and is a specific target for tumor suppressor p53binding protein 1, a conserved checkpoint protein with properties of a DNA DSB sensor [49].”
BackgroundThe many faces of ubiquitinated histone H2A: insights from the DUBs
Vissers, J. H. A., Nicassio, F., van Lohuizen, M., Fiore, P. P. D., & Citterio, E. (2008) · Cell Division · doi:10.1186/1747-1028-3-8 · Cited by 83
“This mechanism might be relevant for 53BP1 relocalization to IRIF, as suggested by the findings that 53BP1 binds to methylated histones [ 72 ,73] and that its recruitment is independent from Rap80 [18,19,55,68].”
BackgroundBarreto-Andrade, J. C., Efimova, E. V., Mauceri, H. J., Beckett, M. A., Sutton, H. G., Darga, T. E., Vokes, E. E., Posner, M. C., Kron, S. J., & Weichselbaum, R. R. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-11-0061 · Cited by 83
“Histone 2A, member X (gH2AX) and p53 binding protein 1 (53BP1) localization to IR-induced foci (IRIF) can serve as proxies for unrepaired DSBs and the DNA damage response (33, 34).”
The multifunctional human p100 protein 'hooks' methylated ligands
Shaw, N., Zhao, M., Cheng, C., Xu, H., Saarikettu, J., Li, Y., Da, Y., Yao, Z., Silvennoinen, O., Yang, J., et al. (2007) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1269 · Cited by 81
Role of Deubiquitinating Enzymes in DNA Repair
Kee, Y., & Huang, T. T. (2015) · Molecular and Cellular Biology · doi:10.1128/mcb.00847-15 · Cited by 81
“How do K63 chains at DSB sites promote NHEJ repair? A key factor recruited to the DSB sites is 53BP1, which possesses a TUDOR domain (protein structural motif originally identified as a region of 50 amino acids found in the Tudor protein encoded by genes in Drosophila melanogaster that binds methylated histone H3 (40)…”
BackgroundDistinct versus overlapping functions of MDC1 and 53BP1 in DNA damage response and tumorigenesis
Minter‐Dykhouse, K., Ward, I. M., Huen, M. S. Y., Chen, J., & Lou, Z. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200801083 · Cited by 82
“The online version of this article contains supplemental material.”
BackgroundThe Tandem BRCT Domain of 53BP1 Is Not Required for Its Repair Function
Ward, I. M., Kim, J., Minn, K. T., Chini, C. C. S., Mer, G., & Chen, J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m607577200 · Cited by 80
Barry, E., Krueger, W. H., Jakuba, C. M., Veilleux, E. S., Ambrosi, D. J., Nelson, C. E., & Rasmussen, T. P. (2009) · Stem Cells · doi:10.1002/stem.86 · Cited by 83
Complex engagement of DNA damage response pathways in human cancer and in lung tumor progression
Nuciforo, P. G., Luise, C., Capra, M. C., Pelosi, G., & di Fagagna, F. D. (2007) · Carcinogenesis · doi:10.1093/carcin/bgm108 · Cited by 80
Histone Methyltransferase DOT1L Drives Recovery of Gene Expression after a Genotoxic Attack
Oksenych, V., Zhovmer, A. S., Ziani, S., Mari, P., Eberová, J., Nardò, T., Stefanini, M., Giglia‐Mari, G., Egly, J., & Coin, F. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003611 · Cited by 78
“DOT1L has been reported to favor the recruitment of double strand breaks sensor 53BP1 to DNA lesions [18].”
BackgroundTudor and its domains: germ cell formation from a Tudor perspective
Thomson, T., & Lasko, P. F. (2005) · Cell Research · doi:10.1038/sj.cr.7290297 · Cited by 79
Bock, I., Kudithipudi, S., Tamas, R., Kungulovski, G., Dhayalan, A., & Jeltsch, A. (2011) · BMC Biochemistry · doi:10.1186/1471-2091-12-48 · Cited by 83
Wang, Q., & Goldstein, M. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-2334 · Cited by 78
Gieni, R. S., Ismail, I. H., Campbell, S., & Hendzel, M. J. (2011) · Cell Cycle · doi:10.4161/cc.10.6.14907 · Cited by 71
The Chromatin Response to Double-Strand DNA Breaks and Their Repair
Aleksandrov, R., Hristova, R. H., Stoynov, S., & Gospodinov, A. G. (2020) · Cells · doi:10.3390/cells9081853 · Cited by 79
Cheng, W., Muftic, D., Müftüoğlu, M., Dawut, L., Morris, C., Helleday, T., Shiloh, Y., & Bohr, V. A. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-07-0698 · Cited by 81
Hwang, J. W., Kim, S., Myung, N., Song, D., Han, G., Bae, G., Bedford, M. T., & Kim, Y. K. (2020) · Communications Biology · doi:10.1038/s42003-020-01157-z · Cited by 81
Radiosensitivity in breast cancer assessed by the histone γ-H2AX and 53BP1 foci
Djuzenova, C. S., Elsner, I., Katzer, A., Worschech, E., Distel, L. V., Flentje, M. P., & Polat, B. (2013) · Radiation Oncology · doi:10.1186/1748-717x-8-98 · Cited by 75
DOT1L Inhibition Sensitizes MLL-Rearranged AML to Chemotherapy
Liu, W., Deng, L., Song, Y., & Redell, M. S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0098270 · Cited by 76
“Since H3K79 methylation is reported to be involved in the DNA damage response [14], we reasoned that SYC-522 might impair chemotherapy-induced DNA damage signaling.”
BackgroundInfluentialRAD18 promotes DNA double-strand break repair during G1 phase through chromatin retention of 53BP1
Watanabe, K., Iwabuchi, K., Sun, J., Tsuji, Y., Tani, T., Tokunaga, K., Date, T., HASHIMOTO, M. W., Yamaizumi, M., & Tateishi, S. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp082 · Cited by 75
“In the cellular response to IR, the exposure of methylated histones is required for the initial recruitment of 53BP1 to DSBs (20,21).”
Li, X., Isono, K., Yamada, D., Endo, T. A., Endoh, M., Shinga, J., Mizutani-Koseki, Y., Otte, A. P., Casanova, M., Kitamura, H., et al. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.00259-10 · Cited by 80
“In addition to detection of the methylation status of histone tails, Tudor and PHD finger domains have also been shown to contribute to recognition of RNA and phosphatidylinositols, respectively (7, 22, 26).”
BackgroundTying the loose ends together in DNA double strand break repair with 53BP1.
Adams, M. M., & Carpenter, P. B. (2006) · Cell Division · doi:10.1186/1747-1028-1-19 · Cited by 77
“Linking 53BP1 function with chromatin structure Although unlikely to be a structural component of chromatin, 53BP1 possesses several intriguing links to the biology of chromatin, particularly with respect to the regulation of histone modifications [59, 60 ].”
BackgroundInfluentialUsui, T., Foster, S. S., & Petrini, J. H. J. (2009) · Molecular Cell · doi:10.1016/j.molcel.2008.12.022 · Cited by 81
“These HM-dependent mechanisms of Rad9 binding appear to be conserved in Crb2 and 53BP1, the Rad9 orthologs in S. pombe and mammals (Botuyan et al., 2006; Celeste et al., 2002; Du et al., 2006; Huyen et al., 2004; Nakamura et al., 2004; Sanders et al., 2004).”
BackgroundRNF20–RNF40: A ubiquitin‐driven link between gene expression and the DNA damage response
Shiloh, Y., Shema, E., Moyal, L., & Oren, M. (2011) · FEBS Letters · doi:10.1016/j.febslet.2011.07.034 · Cited by 77
“posed due to alterations in chromatin organization at these sites [104,106,108].”
BackgroundKurose, A., Tanaka, T., Huang, X., Halicka, H. D., Traganos, F., Dai, W. H., & Darżynkiewicz, Z. (2005) · Cytometry Part A · doi:10.1002/cyto.a.20186 · Cited by 74
Epigenetic regulation of genomic integrity
Deem, A. K., Li, X., & Tyler, J. K. (2012) · Chromosoma · doi:10.1007/s00412-011-0358-1 · Cited by 78
“However, 53BP1 does not bind directly to ubiquitin chains; rather, it binds via tandem TUDOR domains to dimethylated lysine K20 on histone H4 (Botuyan et al. 2006; Huyen et al. 2004).”
The role of RAD6 in recombinational repair, checkpoints and meiosis via histone modification
Game, J. C., & Chernikova, S. B. (2009) · DNA repair · doi:10.1016/j.dnarep.2009.01.007 · Cited by 73
Hammack, C., Ogden, S. C., Madden, J. C., Medina, A., Xu, C., Phillips, E. O. N., Son, Y., Cone, A. S., Giovinazzi, S., Didier, R., et al. (2019) · Journal of Virology · doi:10.1128/jvi.00638-19 · Cited by 73
Menin “reads” H3K79me2 mark in a nucleosomal context
Lin, J., Wu, Y., Tian, G., Yu, D., Yang, E., Lam, W. H., Liu, Z., Jing, Y., Dang, S., Bao, X., et al. (2023) · Science · doi:10.1126/science.adc9318 · Cited by 71
Structural dynamics of protein lysine methylation and demethylation
Cheng, X., & Zhang, X. (2007) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2006.05.041 · Cited by 73
Qin, S., & Parthun, M. R. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.9.3649-3658.2006 · Cited by 72
“In addition, while not induced by DNA damage, methylation of histone H3 K79 (or histone H4 K20 in Schizosaccharomyces pombe) is also involved in the DNA damage checkpoint through the recruitment of the checkpoint proteins 53BP1/Rad9p/Crb2 (15, 18 , 38).”
BackgroundZhou, L., Holt, M. T., Ohashi, N., Zhao, A., Müller, M. M., Wang, B., & Muir, T. W. (2016) · Nature Communications · doi:10.1038/ncomms10589 · Cited by 72
“(d) SDS-PAGE analysis of crosslinked reaction mixtures of mononucleosomes containing H2BssUb* and either full-length H2A, H2AD(1-10) or H2AD(1-15).”
Lee, J., Gold, D. A., Shevchenko, A., Shevchenko, A., & Dunphy, W. G. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-07-0671 · Cited by 72
“Crb2 recognize methylated forms of lysine 79 in histone H3 and lysine 20 in histone H4, respectively (Huyen et al., 2004; Sanders et al., 2004).”
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
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