• This record comes from PubMed

H3K9me3 and H4K20me3 represent the epigenetic landscape for 53BP1 binding to DNA lesions

. 2018 Oct 11 ; 10 (10) : 2585-2605.

Language English Country United States Media print

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/pmid30312172

Methylation of histones H4 at lysine 20 position (H4K20me), which is functional in DNA repair, represents a binding site for the 53BP1 protein. Here, we show a radiation-induced increase in the level of H4K20me3 while the levels of H4K20me1 and H4K20me2 remained intact. H4K20me3 was significantly pronounced at DNA lesions in only the G1 phase of the cycle, while this histone mark was reduced in very late S and G2 phases when PCNA was recruited to locally micro-irradiated chromatin. H4K20me3 was diminished in locally irradiated Suv39h1/h2 double knockout (dn) fibroblasts, and the same phenomenon was observed for H3K9me3 and its binding partner, the HP1β protein. Immunoprecipitation showed the existence of an interaction between H3K9me3-53BP1 and H4K20me3-53BP1; however, HP1β did not interact with 53BP1. Together, H3K9me3 and H4K20me3 represent epigenetic markers that are important for the function of the 53BP1 protein in non-homologous end joining (NHEJ) repair. The very late S phase represents the cell cycle breakpoint when a DDR function of the H4K20me3-53BP1 complex is abrogated due to recruitment of the PCNA protein and other DNA repair factors of homologous recombination to DNA lesions.

See more in PubMed

Goodarzi AA, Jeggo PA. The heterochromatic barrier to DNA double strand break repair: how to get the entry visa. Int J Mol Sci. 2012; 13:11844–60. 10.3390/ijms130911844 PubMed DOI PMC

Friedberg EC, Aguilera A, Gellert M, Hanawalt PC, Hays JB, Lehmann AR, Lindahl T, Lowndes N, Sarasin A, Wood RD. DNA repair: from molecular mechanism to human disease. DNA Repair (Amst). 2006; 5:986–96. 10.1016/j.dnarep.2006.05.005 PubMed DOI

Suchánková J, Legartová S, Ručková E, Vojtěšek B, Kozubek S, Bártová E. Mutations in the TP53 gene affected recruitment of 53BP1 protein to DNA lesions, but level of 53BP1 was stable after γ-irradiation that depleted MDC1 protein in specific TP53 mutants. Histochem Cell Biol. 2017; 148:239–55. 10.1007/s00418-017-1567-3 PubMed DOI

Kinner A, Wu W, Staudt C, Iliakis G. γ-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin. Nucleic Acids Res. 2008; 36:5678–94. 10.1093/nar/gkn550 PubMed DOI PMC

Bártová E, Kozubek S, Kozubek M, Jirsová P, Lukásová E, Skalníková M, Buchnícková K. The influence of the cell cycle, differentiation and irradiation on the nuclear location of the abl, bcr and c-myc genes in human leukemic cells. Leuk Res. 2000; 24:233–41. 10.1016/S0145-2126(99)00174-5 PubMed DOI

Legartová S, Kozubek S, Franek M, Zdráhal Z, Lochmanová G, Martinet N, Bártová E. Cell differentiation along multiple pathways accompanied by changes in histone acetylation status. Biochem Cell Biol. 2014; 92:85–93. 10.1139/bcb-2013-0082 PubMed DOI

Bártová E, Foltánková V, Legartová S, Sehnalová P, Sorokin DV, Suchánková J, Kozubek S. Coilin is rapidly recruited to UVA-induced DNA lesions and γ-radiation affects localized movement of Cajal bodies. Nucleus. 2014; 5:460–68. 10.4161/nucl.29229 PubMed DOI PMC

Sharma P, Jha AB, Dubey RS, Pessarakli M. Reactive oxygen species, oxidative damage, and antioxidative defense mechanism in plants under stressful conditions. J Bot. 2012; 2012 10.1155/2012/217037 DOI

Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem. 1998; 273:5858–68. 10.1074/jbc.273.10.5858 PubMed DOI

Huyen Y, Zgheib O, Ditullio RA Jr, Gorgoulis VG, Zacharatos P, Petty TJ, Sheston EA, Mellert HS, Stavridi ES, Halazonetis TD. Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks. Nature. 2004; 432:406–11. 10.1038/nature03114 PubMed DOI

Botuyan MV, Lee J, Ward IM, Kim JE, Thompson JR, Chen J, Mer G. Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair. Cell. 2006; 127:1361–73. 10.1016/j.cell.2006.10.043 PubMed DOI PMC

Schotta G, Lachner M, Sarma K, Ebert A, Sengupta R, Reuter G, Reinberg D, Jenuwein T. A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin. Genes Dev. 2004; 18:1251–62. 10.1101/gad.300704 PubMed DOI PMC

Wang Z, Zang C, Rosenfeld JA, Schones DE, Barski A, Cuddapah S, Cui K, Roh TY, Peng W, Zhang MQ, Zhao K. Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet. 2008; 40:897–903. 10.1038/ng.154 PubMed DOI PMC

Sanders SL, Portoso M, Mata J, Bähler J, Allshire RC, Kouzarides T. Methylation of histone H4 lysine 20 controls recruitment of Crb2 to sites of DNA damage. Cell. 2004; 119:603–14. 10.1016/j.cell.2004.11.009 PubMed DOI

Pei H, Zhang L, Luo K, Qin Y, Chesi M, Fei F, Bergsagel PL, Wang L, You Z, Lou Z. MMSET regulates histone H4K20 methylation and 53BP1 accumulation at DNA damage sites. Nature. 2011; 470:124–28. 10.1038/nature09658 PubMed DOI PMC

Hajdu I, Ciccia A, Lewis SM, Elledge SJ. Wolf-Hirschhorn syndrome candidate 1 is involved in the cellular response to DNA damage. Proc Natl Acad Sci USA. 2011; 108:13130–34. 10.1073/pnas.1110081108 PubMed DOI PMC

Bromberg KD, Mitchell TR, Upadhyay AK, Jakob CG, Jhala MA, Comess KM, Lasko LM, Li C, Tuzon CT, Dai Y, Li F, Eram MS, Nuber A, et al.. The SUV4-20 inhibitor A-196 verifies a role for epigenetics in genomic integrity. Nat Chem Biol. 2017; 13:317–24. 10.1038/nchembio.2282 PubMed DOI

Li J, Xu X. DNA double-strand break repair: a tale of pathway choices. Acta Biochim Biophys Sin (Shanghai). 2016; 48:641–46. 10.1093/abbs/gmw045 PubMed DOI

Pellegrino S, Michelena J, Teloni F, Imhof R, Altmeyer M. Replication-coupled dilution of H4K20me2 guides 53BP1 to pre-replicative chromatin. Cell Reports. 2017; 19:1819–31. 10.1016/j.celrep.2017.05.016 PubMed DOI PMC

Simonetta M, de Krijger I, Serrat J, Moatti N, Fortunato D, Hoekman L, Bleijerveld OB, Altelaar AF, Jacobs JJ. H4K20me2 distinguishes pre-replicative from post-replicative chromatin to appropriately direct DNA repair pathway choice by 53BP1-RIF1-MAD2L2. Cell Cycle. 2018; 17:124–36. 10.1080/15384101.2017.1404210 PubMed DOI PMC

Drané P, Brault ME, Cui G, Meghani K, Chaubey S, Detappe A, Parnandi N, He Y, Zheng XF, Botuyan MV, Kalousi A, Yewdell WT, Münch C, et al.. TIRR regulates 53BP1 by masking its histone methyl-lysine binding function. Nature. 2017; 543:211–16. 10.1038/nature21358 PubMed DOI PMC

Tang J, Cho NW, Cui G, Manion EM, Shanbhag NM, Botuyan MV, Mer G, Greenberg RA. Acetylation limits 53BP1 association with damaged chromatin to promote homologous recombination. Nat Struct Mol Biol. 2013; 20:317–25. 10.1038/nsmb.2499 PubMed DOI PMC

Fradet-Turcotte A, Canny MD, Escribano-Díaz C, Orthwein A, Leung CC, Huang H, Landry MC, Kitevski-LeBlanc J, Noordermeer SM, Sicheri F, Durocher D. 53BP1 is a reader of the DNA-damage-induced H2A Lys 15 ubiquitin mark. Nature. 2013; 499:50–54. 10.1038/nature12318 PubMed DOI PMC

Bannister AJ, Kouzarides T. Reversing histone methylation. Nature. 2005; 436:1103–06. 10.1038/nature04048 PubMed DOI

Ayrapetov MK, Gursoy-Yuzugullu O, Xu C, Xu Y, Price BD. DNA double-strand breaks promote methylation of histone H3 on lysine 9 and transient formation of repressive chromatin. Proc Natl Acad Sci USA. 2014; 111:9169–74. 10.1073/pnas.1403565111 PubMed DOI PMC

Sun Y, Jiang X, Xu Y, Ayrapetov MK, Moreau LA, Whetstine JR, Price BD. Histone H3 methylation links DNA damage detection to activation of the tumour suppressor Tip60. Nat Cell Biol. 2009; 11:1376–82. 10.1038/ncb1982 PubMed DOI PMC

Harnicarová Horáková A, Galiová G, Legartová S, Kozubek S, Matula P, Bártová E. Chromocentre integrity and epigenetic marks. J Struct Biol. 2010; 169:124–33. 10.1016/j.jsb.2009.09.007 PubMed DOI

Fodor BD, Kubicek S, Yonezawa M, O’Sullivan RJ, Sengupta R, Perez-Burgos L, Opravil S, Mechtler K, Schotta G, Jenuwein T. Jmjd2b antagonizes H3K9 trimethylation at pericentric heterochromatin in mammalian cells. Genes Dev. 2006; 20:1557–62.10.1101/gad.388206 PubMed DOI PMC

Bártová E, Lochmanová G, Legartová S, Suchánková J, Fedr R, Krejčí J, Zdráhal Z. Irradiation by γ-rays reduces the level of H3S10 phosphorylation and weakens the G2 phase-dependent interaction between H3S10 phosphorylation and γH2AX. Biochimie. 2018; 154:86–98.10.1016/j.biochi.2018.07.029 PubMed DOI

Bártová E, Malyšková B, Komůrková D, Legartová S, Suchánková J, Krejčí J, Kozubek S. Function of heterochromatin protein 1 during DNA repair. Protoplasma. 2017; 254:1233–40. 10.1007/s00709-017-1090-3 PubMed DOI

Luijsterburg MS, Dinant C, Lans H, Stap J, Wiernasz E, Lagerwerf S, Warmerdam DO, Lindh M, Brink MC, Dobrucki JW, Aten JA, Fousteri MI, Jansen G, et al.. Heterochromatin protein 1 is recruited to various types of DNA damage. J Cell Biol. 2009; 185:577–86. 10.1083/jcb.200810035 PubMed DOI PMC

Stixová L, Sehnalová P, Legartová S, Suchánková J, Hrušková T, Kozubek S, Sorokin DV, Matula P, Raška I, Kovařík A, Fulneček J, Bártová E. HP1β-dependent recruitment of UBF1 to irradiated chromatin occurs simultaneously with CPDs. Epigenetics Chromatin. 2014; 7:39. 10.1186/1756-8935-7-39 PubMed DOI PMC

Polo SE, Jackson SP. Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications. Genes Dev. 2011; 25:409–33. 10.1101/gad.2021311 PubMed DOI PMC

Hsiao KY, Mizzen CA. Histone H4 deacetylation facilitates 53BP1 DNA damage signaling and double-strand break repair. J Mol Cell Biol. 2013; 5:157–65. 10.1093/jmcb/mjs066 PubMed DOI

Suchánková J, Kozubek S, Legartová S, Sehnalová P, Küntziger T, Bártová E. Distinct kinetics of DNA repair protein accumulation at DNA lesions and cell cycle-dependent formation of γH2AX- and NBS1-positive repair foci. Biol Cell. 2015; 107:440–54. 10.1111/boc.201500050 PubMed DOI

Wakeman TP, Wang Q, Feng J, Wang XF. Bat3 facilitates H3K79 dimethylation by DOT1L and promotes DNA damage-induced 53BP1 foci at G1/G2 cell-cycle phases. EMBO J. 2012; 31:2169–81. 10.1038/emboj.2012.50 PubMed DOI PMC

Tong Q, Cui G, Botuyan MV, Rothbart SB, Hayashi R, Musselman CA, Singh N, Appella E, Strahl BD, Mer G, Kutateladze TG. Structural plasticity of methyllysine recognition by the tandem tudor domain of 53BP1. Structure. 2015; 23:312–21. 10.1016/j.str.2014.11.013 PubMed DOI PMC

Bannister AJ, Zegerman P, Partridge JF, Miska EA, Thomas JO, Allshire RC, Kouzarides T. Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature. 2001; 410:120–24. 10.1038/35065138 PubMed DOI

Sharma GG, So S, Gupta A, Kumar R, Cayrou C, Avvakumov N, Bhadra U, Pandita RK, Porteus MH, Chen DJ, Cote J, Pandita TK. MOF and histone H4 acetylation at lysine 16 are critical for DNA damage response and double-strand break repair. Mol Cell Biol. 2010; 30:3582–95. 10.1128/MCB.01476-09 PubMed DOI PMC

Li X, Corsa CA, Pan PW, Wu L, Ferguson D, Yu X, Min J, Dou Y. MOF and H4 K16 acetylation play important roles in DNA damage repair by modulating recruitment of DNA damage repair protein Mdc1. Mol Cell Biol. 2010; 30:5335–47. 10.1128/MCB.00350-10 PubMed DOI PMC

Southall SM, Cronin NB, Wilson JR. A novel route to product specificity in the Suv4-20 family of histone H4K20 methyltransferases. Nucleic Acids Res. 2014; 42:661–71. 10.1093/nar/gkt776 PubMed DOI PMC

Cheutin T, McNairn AJ, Jenuwein T, Gilbert DM, Singh PB, Misteli T. Maintenance of stable heterochromatin domains by dynamic HP1 binding. Science. 2003; 299:721–25. 10.1126/science.1078572 PubMed DOI

Franek M, Kovaříková A, Bártová E, Kozubek S. Nucleolar reorganization upon site-specific double-strand break induction: DNA repair and epigenetics of ribosomal genes. J Histochem Cytochem. 2016; 64:669–86. 10.1369/0022155416668505 PubMed DOI PMC

Legartová S, Suchánková J, Krejčí J, Kovaříková A, Bártová E. Advanced confocal microscopy techniques to study protein-protein interactions and kinetics at DNA l esions. J Vis Exp. 2017. 10.3791/55999 PubMed DOI PMC

Sehnalová P, Legartová S, Cmarko D, Kozubek S, Bártová E. Recruitment of HP1β to UVA-induced DNA lesions is independent of radiation-induced changes in A-type lamins. Biol Cell. 2014; 106:151–65. 10.1111/boc.201300076 PubMed DOI

Find record

Citation metrics

Archiving options