Early recruitment of PARP-dependent m⁸A RNA methylation at DNA lesions is subsequently accompanied by active DNA demethylation

References

• Hirota K, Ooka M, Shimizu N, et al. XRCC1 counteracts poly(ADP ribose)polymerase (PARP) poisons, olaparib and talazoparib, and a clinical alkylating agent, temozolomide, by promoting the removal of trapped PARP1 from broken DNA. Genes Cells. 2022;27:331–344.
   PubMed Web of Science ®Google Scholar
• Essers J, Theil AF, Baldeyron C, et al. Nuclear dynamics of PCNA in DNA replication and repair. Mol Cell Biol. 2005;25:9350–9359.
   PubMed Web of Science ®Google Scholar
• Cappelli E, Taylor R, Cevasco M, et al. Involvement of XRCC1 and DNA ligase III gene products in DNA base excision repair. J Biol Chem. 1997;272:23970–23975.
   PubMed Web of Science ®Google Scholar
• Pascucci B, Stucki M, Jonsson ZO, et al. Long patch base excision repair with purified human proteins. DNA ligase I as patch size mediator for DNA polymerases delta and epsilon. J Biol Chem. 1999;274:33696–33702.
   PubMed Web of Science ®Google Scholar
• Shuck SC, Short EA, Turchi JJ. Eukaryotic nucleotide excision repair: from understanding mechanisms to influencing biology. Cell Res. 2008;18:64–72.
   PubMed Web of Science ®Google Scholar
• G-M L. Mechanisms and functions of DNA mismatch repair. Cell Res. 2008;18(1):85–98.
   PubMed Web of Science ®Google Scholar
• Mao Z, Bozzella M, Seluanov A, et al. Comparison of nonhomologous end joining and homologous recombination in human cells. DNA Repair (Amst). 2008;7:1765–1771.
   PubMed Web of Science ®Google Scholar
• Shrivastav M, De Haro LP, Nickoloff JA. Regulation of DNA double-strand break repair pathway choice. Cell Res. 2008;18(1):134–147.
   PubMed Web of Science ®Google Scholar
• Isono M, Niimi A, Oike T, et al. BRCA1 directs the repair pathway to homologous recombination by promoting 53BP1 dephosphorylation. Cell Rep. 2017;18:520–532.
   PubMed Web of Science ®Google Scholar
• Li S, Chen P-L, Subramanian T, et al. Binding of ctIP to the BRCT repeats of BRCA1 involved in the transcription regulation of p21 is disrupted upon DNA Damage. J Biol Chem. 1999;274(16):11334–11338.
   PubMed Web of Science ®Google Scholar
• Shinohara M, Bishop DK, Shinohara A. Distinct functions in regulation of meiotic crossovers for DNA damage response clamp loader rad24(Rad17) and Mec1(ATR) kinase. Genetics. 2019;213(4):1255–1269.
   PubMed Web of Science ®Google Scholar
• Hartlerode AJ, Guan Y, Rajendran A, et al. Impact of histone H4 lysine 20 methylation on 53BP1 responses to chromosomal double strand breaks. PLoS One. 2012;7(11):e49211.
   PubMed Web of Science ®Google Scholar
• Hsiao KY, Mizzen CA. Histone H4 deacetylation facilitates 53BP1 DNA damage signaling and double-strand break repair. J Mol Cell Biol. 2013;5:157–165.
   PubMed Web of Science ®Google Scholar
• Ataian Y, Krebs JE. Five repair pathways in one context: chromatin modification during DNA repair. Biochem Cell Biol. 2006;84:490–504.
   PubMedGoogle Scholar
• Bao Y. Chromatin response to DNA double-strand break damage. Epigenomics. 2011;3:307–321.
   PubMed Web of Science ®Google Scholar
• Downs JA, Allard S, Jobin-Robitaille O, et al. Binding of chromatin-modifying activities to phosphorylated histone H2A at DNA damage sites. Mol Cell. 2004;16:979–990.
   PubMed Web of Science ®Google Scholar
• Rogakou EP, Pilch DR, Orr AH, et al. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem. 1998;273:5858–5868.
   PubMed Web of Science ®Google Scholar
• Svobodova Kovarikova A, Legartova S, Krejci J, et al. H3K9me3 and H4K20me3 represent the epigenetic landscape for 53BP1 binding to DNA lesions. Aging (Albany NY). 2018;10:2585–2605.
   PubMedGoogle Scholar
• Game JC, Chernikova SB. The role of RAD6 in recombinational repair, checkpoints and meiosis via histone modification. DNA Repair (Amst). 2009;8:470–482.
   PubMed Web of Science ®Google Scholar
• Game JC, Williamson MS, Baccari C. X-ray survival characteristics and genetic analysis for nine Saccharomyces deletion mutants that show altered radiation sensitivity. Genetics. 2005;169:51–63.
   PubMed Web of Science ®Google Scholar
• Game JC, Williamson MS, Spicakova T, et al. The RAD6/BRE1 histone modification pathway in Saccharomyces confers radiation resistance through a RAD51-dependent process that is independent of RAD18. Genetics. 2006;173:1951–1968.
   PubMed Web of Science ®Google Scholar
• Grenon M, Costelloe T, Jimeno S, et al. Docking onto chromatin via the Saccharomyces cerevisiae Rad9 Tudor domain. Yeast. 2007;24:105–119.
   PubMed Web of Science ®Google Scholar
• Ikura T, Ogryzko VV, Grigoriev M, et al. Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis. Cell. 2000;102:463–473.
   PubMed Web of Science ®Google Scholar
• Murr R, Loizou JI, Yang YG, et al. Histone acetylation by Trrap-Tip60 modulates loading of repair proteins and repair of DNA double-strand breaks. Nat Cell Biol. 2006;8:91–99.
   PubMed Web of Science ®Google Scholar
• Miller KM, Tjeertes JV, Coates J, et al. Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA nonhomologous end-joining. Nat Struct Mol Biol. 2010;17:1144–1151.
   PubMed Web of Science ®Google Scholar
• Bartova E, Sustackova G, Stixova L, et al. Recruitment of Oct4 protein to UV-damaged chromatin in embryonic stem cells. PLoS One. 2011;6:e27281.
   PubMed Web of Science ®Google Scholar
• Svobodova Kovarikova A, Stixova L, Kovarik A, et al. N(6)-adenosine methylation in RNA and a reduced m3G/TMG level in non-coding RNAs appear at microirradiation-induced DNA lesions. Cells. 2020;9:360.
   PubMed Web of Science ®Google Scholar
• Xiang Y, Laurent B, Hsu CH, et al. RNA m(6)A methylation regulates the ultraviolet-induced DNA damage response. Nature. 2017;543:573–576.
   PubMed Web of Science ®Google Scholar
• Jimeno S, Balestra FR, Huertas P. The emerging role of RNA modifications in DNA double-strand break repair. Front Mol Biosci. 2021;8:664872.
   PubMed Web of Science ®Google Scholar
• Zhang M, Wang L, Zhong D. Photolyase: dynamics and mechanisms of repair of sun-induced DNA damage. Photochem Photobiol. 2017;93:78–92.
   PubMed Web of Science ®Google Scholar
• Zhang C, Chen L, Peng D, et al. METTL3 and N6-methyladenosine promote homologous recombination-mediated repair of DSBs by modulating DNA-RNA hybrid accumulation. Mol Cell. 2020;79:425–42 e7.
   PubMed Web of Science ®Google Scholar
• Costantino L, Koshland D. Genome-wide map of r-loop-induced damage reveals how a subset of r-loops contributes to genomic instability. Mol Cell. 2018;71:487–97 e3.
   PubMed Web of Science ®Google Scholar
• Garcia-Muse T, Aguilera A. R loops: from physiological to pathological roles. Cell. 2019;179:604–618.
   PubMed Web of Science ®Google Scholar
• Ohle C, Tesorero R, Schermann G, et al. Transient RNA-DNA hybrids are required for efficient double-strand break repair. Cell. 2016;167:1001–13 e7.
   PubMed Web of Science ®Google Scholar
• Paull TT. RNA-DNA hybrids and the convergence with DNA repair. Crit Rev Biochem Mol Biol. 2019;54:371–384.
   PubMed Web of Science ®Google Scholar
• Puget N, Miller KM, Legube G. Non-canonical DNA/RNA structures during transcription-coupled double-strand break repair: roadblocks or Bona fide repair intermediates? DNA Repair (Amst). 2019;81:102661.
   PubMed Web of Science ®Google Scholar
• Zhang A, Peng B, Huang P, et al. The p53-binding protein 1-Tudor-interacting repair regulator complex participates in the DNA damage response. J Biol Chem. 2017;292:6461–6467.
   PubMed Web of Science ®Google Scholar
• Qu F, Tsegay PS, Liu Y. N(6)-methyladenosine, DNA repair, and genome stability. Front Mol Biosci. 2021;8:645823.
   PubMed Web of Science ®Google Scholar
• Giessing AM, Jensen SS, Rasmussen A, et al. Identification of 8-methyladenosine as the modification catalyzed by the radical SAM methyltransferase Cfr that confers antibiotic resistance in bacteria. RNA. 2009;15:327–336.
   PubMed Web of Science ®Google Scholar
• Demin AA, Hirota K, Tsuda M, et al. XRCC1 prevents toxic PARP1 trapping during DNA base excision repair. Mol Cell. 2021;81:3018–30 e5.
   PubMed Web of Science ®Google Scholar
• Fisher AE, Hochegger H, Takeda S, et al. Poly(ADP-ribose) polymerase 1 accelerates single-strand break repair in concert with poly(ADP-ribose) glycohydrolase. Mol Cell Biol. 2007;27:5597–5605.
   PubMed Web of Science ®Google Scholar
• Kutuzov MM, Belousova EA, Kurgina TA, et al. The contribution of PARP1, PARP2 and poly(ADP-ribosyl)ation to base excision repair in the nucleosomal context. Sci Rep. 2021;11:4849.
   PubMed Web of Science ®Google Scholar
• Ström CE, Johansson F, Uhlén M, et al. Poly (ADP-ribose) polymerase (PARP) is not involved in base excision repair but PARP inhibition traps a single-strand intermediate. Nucleic Acids Res. 2010;39:3166–3175.
   PubMed Web of Science ®Google Scholar
• Murai J, Huang SY, Das BB, et al. Trapping of PARP1 and PARP2 by clinical PARP inhibitors. Cancer Res. 2012;72:5588–5599.
   PubMed Web of Science ®Google Scholar
• Zhang J. Brothers in arms: emerging roles of RNA epigenetics in DNA damage repair. Cell Biosci. 2017;7:24.
   PubMed Web of Science ®Google Scholar
• Bromberg KD, Mitchell TR, Upadhyay AK, et al. The SUV4-20 inhibitor A-196 verifies a role for epigenetics in genomic integrity. Nat Chem Biol. 2017;13:317–324.
   PubMed Web of Science ®Google Scholar
• Paquin KL, Howlett NG. Understanding the histone DNA repair code: H4K20me2 makes its mark. Mol Cancer Res. 2018;16:1335–1345.
   PubMed Web of Science ®Google Scholar
• Suchankova J, Kozubek S, Legartova S, et al. Distinct kinetics of DNA repair protein accumulation at DNA lesions and cell cycle-dependent formation of gammaH2AX- and NBS1-positive repair foci. Biol Cell. 2015;107:440–454.
   PubMed Web of Science ®Google Scholar
• Budhavarapu VN, Chavez M, Tyler JK. How is epigenetic information maintained through DNA replication? Epigenetics Chromatin. 2013;6:32.
   PubMed Web of Science ®Google Scholar
• Bartova E, Legartova S, Dundr M, et al. A role of the 53BP1 protein in genome protection: structural and functional characteristics of 53BP1-dependent DNA repair. Aging (Albany NY). 2019;11:2488–2511.
   PubMedGoogle Scholar
• Yankova E, Blackaby W, Albertella M, et al. Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia. Nature. 2021;593:597–601.
   PubMed Web of Science ®Google Scholar
• Poczta A, Rogalska A, Marczak A. Treatment of multiple myeloma and the role of melphalan in the era of modern therapies-current research and clinical approaches. J Clin Med. 2021;10:1841.
   PubMed Web of Science ®Google Scholar
• Sehnalova P, Legartova S, Cmarko D, et al. Recruitment of HP1beta to UVA-induced DNA lesions is independent of radiation-induced changes in A-type lamins. Biol Cell. 2014;106:151–165.
   PubMed Web of Science ®Google Scholar
• San Martin Alonso M, Noordermeer SM. Untangling the crosstalk between BRCA1 and R-loops during DNA repair. Nucleic Acids Res. 2021;49:4848–4863.
   PubMed Web of Science ®Google Scholar
• Suchankova J, Legartova S, Ruckova E, et al. Mutations in the TP53 gene affected recruitment of 53BP1 protein to DNA lesions, but level of 53BP1 was stable after gamma-irradiation that depleted MDC1 protein in specific TP53 mutants. Histochem Cell Biol. 2017;148:239–255.
   PubMed Web of Science ®Google Scholar
• Yu D, Horton JR, Yang J, et al. Human MettL3-MettL14 RNA adenine methyltransferase complex is active on double-stranded DNA containing lesions. Nucleic Acids Res. 2021;49:11629–11642.
   PubMed Web of Science ®Google Scholar
• Caron MC, Sharma AK, O’Sullivan J, et al. Poly(ADP-ribose) polymerase-1 antagonizes DNA resection at double-strand breaks. Nat Commun. 2019;10:2954.
   PubMed Web of Science ®Google Scholar
• Trott DA, Porter AC. Hypothesis: transcript-templated repair of DNA double-strand breaks. Bioessays. 2006;28:78–83.
   PubMed Web of Science ®Google Scholar
• Vågbø CB, Slupphaug G. RNA in DNA repair. DNA Repair (Amst). 2020;95:102927.
   PubMed Web of Science ®Google Scholar
• Domingo-Prim J, Bonath F, Visa N. RNA at DNA double-strand breaks: the challenge of dealing with DNA:RNA hybrids. Bioessays. 2020;42:e1900225.
   PubMed Web of Science ®Google Scholar
• Lu S, Dong W, Zhao P, et al. lncRNA FAM83H-AS1 is associated with the prognosis of colorectal carcinoma and promotes cell proliferation by targeting the Notch signaling pathway. Oncol Lett. 2018;15:1861–1868.
   PubMed Web of Science ®Google Scholar
• Noordermeer SM, Adam S, Setiaputra D, et al. The shieldin complex mediates 53BP1-dependent DNA repair. Nature. 2018;560:117–121.
   PubMed Web of Science ®Google Scholar
• Abakir A, Giles TC, Cristini A, et al. N(6)-methyladenosine regulates the stability of RNA:DNA hybrids in human cells. Nat Genet. 2020;52:48–55.
   PubMed Web of Science ®Google Scholar
• Adamowicz M, Hailstone R, Demin AA, et al. XRCC1 protects transcription from toxic PARP1 activity during DNA base excision repair. Nat Cell Biol. 2021;23:1287–1298.
   PubMed Web of Science ®Google Scholar
• Stixova L, Sehnalova P, Legartova S, et al. HP1beta-dependent recruitment of UBF1 to irradiated chromatin occurs simultaneously with CPDs. Epigenetics Chromatin. 2014;7:39.
   PubMed Web of Science ®Google Scholar
• Hegazy YA, Fernando CM, Tran EJ. The balancing act of R-loop biology: the good, the bad, and the ugly. J Biol Chem. 2020;295:905–913.
   PubMed Web of Science ®Google Scholar
• Marnef A, Legube G. m(6)A RNA modification as a new player in R-loop regulation. Nat Genet. 2020;52:27–28.
   PubMed Web of Science ®Google Scholar
• Bartova E, Legartova S, Krejci J, et al. Depletion of A-type lamins and Lap2alpha reduces 53BP1 accumulation at UV-induced DNA lesions and Lap2alpha protein is responsible for compactness of irradiated chromatin. J Cell Biochem. 2018;119:8146–8162.
   PubMed Web of Science ®Google Scholar
• Michelini F, Pitchiaya S, Vitelli V, et al. Damage-induced lncRNAs control the DNA damage response through interaction with DDRNAs at individual double-strand breaks. Nat Cell Biol. 2017;19:1400–1411.
   PubMed Web of Science ®Google Scholar
• Zhu JK. Active DNA demethylation mediated by DNA glycosylases. Annu Rev Genet. 2009;43:143–166.
   PubMed Web of Science ®Google Scholar
• Ito S, Shen L, Dai Q, et al. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science. 2011;333:1300–1303.
   PubMed Web of Science ®Google Scholar
• Zhao H, Zhu M, Limbo O, et al. RNase H eliminates R-loops that disrupt DNA replication but is nonessential for efficient DSB repair. EMBO Rep. 2018;19. DOI:10.15252/embr.201745335
   Web of Science ®Google Scholar
• Horakova AH, Bartova E, Galiova G, et al. SUV39h-independent association of HP1 beta with fibrillarin-positive nucleolar regions. Chromosoma. 2010;119:227–241.
   PubMed Web of Science ®Google Scholar
• Sakaue-Sawano A, Ohtawa K, Hama H, et al. Tracing the silhouette of individual cells in S/G2/M phases with fluorescence. Chem Biol. 2008;15:1243–1248.
   PubMedGoogle Scholar
• Komurkova D, Svobodova Kovarikova A, Bartova E. G-Quadruplex structures colocalize with transcription factories and nuclear speckles surrounded by acetylated and dimethylated histones H3. Int J Mol Sci. 2021;23:22.
   PubMedGoogle Scholar
• Hickson I, Zhao Y, Richardson CJ, et al. Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM. Cancer Res. 2004;64:9152–9159.
   PubMed Web of Science ®Google Scholar
• Yao TT, Mo SM, Liu LY, et al. 5-Aza-2’-deoxycytidine may influence the proliferation and apoptosis of cervical cancer cells via demethylation in a dose- and time-dependent manner. Genet Mol Res. 2013;12:312–318.
   PubMed Web of Science ®Google Scholar
• Stixova L, Bartova E, Matula P, et al. Heterogeneity in the kinetics of nuclear proteins and trajectories of substructures associated with heterochromatin. Epigenetics Chromatin. 2011;4:5.
   PubMed Web of Science ®Google Scholar
• Prasad CB, Prasad SB, Yadav SS, et al. Olaparib modulates DNA repair efficiency, sensitizes cervical cancer cells to cisplatin and exhibits anti-metastatic property. Sci Rep. 2017;7:12876.
   PubMed Web of Science ®Google Scholar
• Spies L, Koekemoer TC, Sowemimo AA, et al. Caspase-dependent apoptosis is induced by Artemisia afra Jacq. ex Willd in a mitochondria-dependent manner after G2/M arrest. S Afr J Bot. 2013;84:104–109.
   Web of Science ®Google Scholar
• Dimitrova N, Chen YC, Spector DL, et al. 53BP1 promotes non-homologous end joining of telomeres by increasing chromatin mobility. Nature. 2008;456:524–528.
   PubMed Web of Science ®Google Scholar
• Luijsterburg MS, Dinant C, Lans H, et al. Heterochromatin protein 1 is recruited to various types of DNA damage. J Cell Biol. 2009;185:577–586.
   PubMed Web of Science ®Google Scholar
• Sustackova G, Kozubek S, Stixova L, et al. Acetylation-dependent nuclear arrangement and recruitment of BMI1 protein to UV-damaged chromatin. J Cell Physiol. 2012;227:1838–1850.
   PubMed Web of Science ®Google Scholar
• Dinant C, de Jager M, Essers J, et al. Activation of multiple DNA repair pathways by sub-nuclear damage induction methods. J Cell Sci. 2007;120:2731–2740.
   PubMed Web of Science ®Google Scholar
• Jawad MM, Qader STA, Zaidan AA, et al. An overview of laser principle, laser-tissue interaction mechanisms and laser safety precautions for medical laser users. Int J Pharmacol. 2011;7:149–160.
   Google Scholar
• Kotsantis P, Silva LM, Irmscher S, et al. Increased global transcription activity as a mechanism of replication stress in cancer. Nat Commun. 2016;7:13087.
   PubMed Web of Science ®Google Scholar
• Legartova S, Lochmanova G, Zdrahal Z, et al. DNA damage changes distribution pattern and levels of HP1 protein isoforms in the nucleolus and increases phosphorylation of HP1beta-Ser88. Cells. 2019;1097:8.
   Google Scholar
• Kumar S, Alibhai D, Margineanu A, et al. FLIM FRET technology for drug discovery: automated multiwell-plate high-content analysis, multiplexed readouts and application in situ. Chemphyschem. 2011;12:609–626.
   PubMed Web of Science ®Google Scholar
• Lakowicz JR, Gryczynski Z. High throughput screening with multiphoton excitation. J Biomol Screen. 1999;4:355–362.
   PubMedGoogle Scholar
• Sillen A, Engelborghs Y. The correct use of “average” fluorescence parameters. Photochem Photobiol. 1998;67:475–486.
   Web of Science ®Google Scholar
• Legartova S, Jugova A, Stixova L, et al. Epigenetic aspects of HP1 exchange kinetics in apoptotic chromatin. Biochimie. 2013;95:167–179.
   PubMed Web of Science ®Google Scholar
• Sedlackova H, Rask MB, Gupta R, et al. Equilibrium between nascent and parental MCM proteins protects replicating genomes. Nature. 2020;587:297–302.
   PubMed Web of Science ®Google Scholar