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DNA damage response and repair pathway modulation by non-histone protein methylation: implications in neurodegeneration

  • Madhusoodanan UrulangodiEmail author
  • Abhishek MohantyEmail author
REVIEW
  • 141 Downloads

Abstract

Protein post-translational modifications (PTMs) have emerged to be combinatorial, essential mechanisms used by eukaryotic cells to regulate local chromatin structure, diversify and extend their protein functions and dynamically coordinate complex intracellular signalling processes. Most common types of PTMs include enzymatic addition of small chemical groups resulting in phosphorylation, glycosylation, poly(ADP-ribosyl)ation, nitrosylation, methylation, acetylation or covalent attachment of complete proteins such as ubiquitin and SUMO. Protein arginine methyltransferases (PRMTs) and protein lysine methyltransferases (PKMTs) enzymes catalyse the methylation of arginine and lysine residues in target proteins, respectively. Rapid progress in quantitative proteomic analysis and functional assays have not only documented the methylation of histone proteins post-translationally but also identified their occurrence in non-histone proteins which dynamically regulate a plethora of cellular functions including DNA damage response and repair. Emerging advances have now revealed the role of both histone and non-histone methylations in the regulating the DNA damage response (DDR) proteins, thereby modulating the DNA repair pathways both in proliferating and post-mitotic neuronal cells. Defects in many cellular DNA repair processes have been found primarily manifested in neuronal tissues. Moreover, fine tuning of the dynamicity of methylation of non-histone proteins as well as the perturbations in this dynamic methylation processes have recently been implicated in neuronal genomic stability maintenance. Considering the impact of methylation on chromatin associated pathways, in this review we attempt to link the evidences in non-histone protein methylation and DDR with neurodegenerative research.

Keywords

DNA damage response DNA repair Non-histone protein methylation Lysine methylation Arginine methylation Neurodegenerative diseases 

Abbreviations

53BP1

p53 binding protein

Amyloid-beta

AD

Alzheimer’s disease

ADMA/Rme2a

Asymmetric dimethylarginine

AID

Activation-Induced cytidine deaminase

ALS

Amyotrophic lateral sclerosis

AOA1

Ataxia-ocular motor Apraxia 1

APTX

Aprataxin

ATLD

Ataxia-telangiectasia like disease

ATM

Ataxia telangiectasia mutated

ATR

Ataxia telangiectasia mutated and Rad3 related

BER

Base excision repair

BRCA1

Breast cancer susceptibility protein 1

BS

Bloom syndrome

CS

Cockayne syndrome

DDR

DNA damage response

DSB

Double strand breaks

ETFβ

Electron transfer flavoprotein

FOXO1

Forkhead transcription factors of class O

FRDA

Friedreich ataxia

FTD

Frontotemporal dementia

FUS/TLS

Fused in sarcoma/Translocated in liposarcoma

FXS

Fragile X syndrome

FXTAS

Fragile X-associated Tremor/Ataxia syndrome

GAR/RGG

Glycine-and-arginine-rich

GG-NER

Global genomic nucleotide excision repair

HD

Huntington’s disease

HP1

Heterochromatin protein 1

HR

Homologous recombination

JMJC

Jumonji domain-containing

MCSZ

Microcephaly with seizures

MMA/Rme1

Monomethylated arginine

MMR

Mismatch repair

MRE11

Meiotic recombination 11

mtDNA

Mitochondrial DNA

NBS

Nijmegen breakage syndrome

NER

Nucleotide excision repair

NFT

Neurofibrillary tangles

NHEJ

Non-homologous end joining

PAD

Protein arginine deiminases

PD

Parkinson’s disease

PKMT

Protein lysine methyltransferases

PNKP

Polynucleotide Kinase/Phosphatase

PRMT

Protein arginine Methyltransferases

PTMs

Post translational modifications

ROS

Reactive oxygen species

RTS

Rothmund–Thomson syndrome

SCAN1

Spinocerebellar ataxia with axonal neuropathy

SDMA/Rme2s

Symmetric dimethylarginine 4

SSB

Single strand breaks

TC-NER

Transcription coupled nucleotide excision repair

TDP1

Tyrosyl DNA-phosphodiesterase 1

TDP-43

TAR DNA binding protein-43

TOP1

Topoisomerase 1

TOP1cc

TOP1 cleavage complex

TTD

Trichothiodystrophy

UBAP2L

Ubiquitin-associated protein 2-like

VHL

von Hippel-Lindau

XP

Xeroderma pigmentosum

WS

Werner syndrome

Notes

Acknowledgments

MU thank Prof. Asha Kishore, Dr. Srinivas G, and Dr. Cibin TR, SCTIMST, for their constant encouragement, stimulating discussion, suggestions and support throughout.

Author contributions

MU and AM equally contributed in conceptualization, writing, and editing the manuscript.

Funding information

MU acknowledge the “seed fund” (#6113) from the Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

References

  1. Agger K, Cloos PA, Christensen J, Pasini D, Rose S, Rappsilber J, Issaeva I, Canaani E, Salcini AE, Helin K (2007) UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development. Nature 449(7163):731–734CrossRefGoogle Scholar
  2. Aguilera A, Garcia-Muse T (2012) R loops: from transcription byproducts to threats to genome stability. Mol Cell 46(2):115–124CrossRefPubMedPubMedCentralGoogle Scholar
  3. Alsulami M, Munawar N, Dillon E, Oliviero G, Wynne K, Alsolami M, Moss C, Ó Gaora P, O'Meara F, Cotter D, Cagney G (2019) SETD1A Methyltransferase is physically and functionally linked to the DNA damage repair protein RAD18. Mol Cell Proteomics 18(7):1428–1436CrossRefPubMedPubMedCentralGoogle Scholar
  4. Alzu A, Bermejo R, Begnis M, Lucca C, Piccini D, Carotenuto W, Saponaro M, Brambati A, Cocito A, Foiani M, Liberi G (2012) Senataxin associates with replication forks to protect fork integrity across RNA-polymerase-II-transcribed genes. Cell 151(4):835–846CrossRefPubMedPubMedCentralGoogle Scholar
  5. Basu U, Meng FL, Keim C, Grinstein V, Pefanis E, Eccleston J, Zhang T, Myers D, Wasserman CR, Wesemann DR, Januszyk K, Gregory RI, Deng H, Lima CD, Alt FW (2011) The RNA exosome targets the AID cytidine deaminase to both strands of transcribed duplex DNA substrates. Cell 144(3):353–363CrossRefPubMedPubMedCentralGoogle Scholar
  6. Bender A, Krishnan KJ, Morris CM, Taylor GA, Reeve AK, Perry RH, Jaros E, Hersheson JS, Betts J, Klopstock T, Taylor RW, Turnbull DM (2006) High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genet 38(5):515–517CrossRefPubMedPubMedCentralGoogle Scholar
  7. Bicker KL, Thompson PR (2013) The protein arginine deiminases: structure, function, inhibition, and disease. Biopolymers 99(2):155–163CrossRefPubMedPubMedCentralGoogle Scholar
  8. Boisvert FM, Dery U, Masson JY, Richard S (2005a) Arginine methylation of MRE11 by PRMT1 is required for DNA damage checkpoint control. Genes Dev 19(6):671–676CrossRefPubMedPubMedCentralGoogle Scholar
  9. Boisvert FM, Rhie A, Richard S, Doherty AJ (2005b) The GAR motif of 53BP1 is arginine methylatedby PRMT1 and is necessary for 53BP1 DNA binding activity. Cell Cycle 4(12):1834–1841CrossRefPubMedPubMedCentralGoogle Scholar
  10. Borgesius NZ, de Waard MC, van der Pluijm I, Omrani A, Zondag GC, van der Horst GT, Melton DW, Hoeijmakers JH, Jaarsma D, Elgersma Y (2011) Accelerated age-related cognitive decline and neurodegeneration, caused by deficient DNA repair. J Neurosci 31(35):12543–12553CrossRefPubMedPubMedCentralGoogle Scholar
  11. Branzei D, Foiani M (2008) Regulation of DNA repair throughout the cell cycle. Nat Rev Mol Cell Biol 9(4):297–308CrossRefPubMedPubMedCentralGoogle Scholar
  12. Branzei D, Szakal B (2016) DNA damage tolerance by recombination: molecular pathways and DNA structures. DNA Repair 44:68–75CrossRefPubMedPubMedCentralGoogle Scholar
  13. Bras J, Alonso I, Barbot C, Costa MM, Darwent L, Orme T, Sequeiros J, Hardy J, Coutinho P, Guerreiro R (2015) Mutations in PNKP cause recessive ataxia with oculomotor apraxia type 4. Am J Hum Genet 96(3):474–479CrossRefPubMedPubMedCentralGoogle Scholar
  14. Brinkmann K, Schell M, Hoppe T, Kashkar H (2015) Regulation of the DNA damage response by ubiquitin conjugation. Front Genet 6:98CrossRefPubMedPubMedCentralGoogle Scholar
  15. Bulau P, Zakrzewicz D, Kitowska K, Wardega B, Kreuder J, Eickelberg O (2006) Quantitative assessment of arginine methylation in free versus protein-incorporated amino acids in vitro and in vivo using protein hydrolysis and high-performance liquid chromatography. BioTechniques 40(3):305–310CrossRefPubMedPubMedCentralGoogle Scholar
  16. Cairns NJ, Neumann M, Bigio EH, Holm IE, Troost D, Hatanpaa KJ, Foong C, White CL 3rd, Schneider JA, Kretzschmar HA, Carter D, Taylor-Reinwald L, Paulsmeyer K, Strider J, Gitcho M, Goate AM, Morris JC, Mishra M, Kwong LK, Stieber A, Xu Y, Forman MS, Trojanowski JQ, Lee VM, Mackenzie IR (2007) TDP-43 in familial and sporadic frontotemporal lobar degeneration with ubiquitin inclusions. Am J Pathol 171(1):227–240CrossRefPubMedPubMedCentralGoogle Scholar
  17. Carney JP, Maser RS, Olivares H, Davis EM, Le Beau M, Yates JR 3rd et al (1998) The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell 93(3):477–486CrossRefPubMedPubMedCentralGoogle Scholar
  18. Carr SM, Munro S, Zalmas LP, Fedorov O, Johansson C, Krojer T, Sagum CA, Bedford MT, Oppermann U, la Thangue NB (2014) Lysine methylation-dependent binding of 53BP1 to the pRb tumor suppressor. Proc Natl Acad Sci U S A 111(31):11341–11346CrossRefPubMedPubMedCentralGoogle Scholar
  19. Ceccaldi R, Rondinelli B, D'Andrea AD (2016) Repair pathway choices and consequences at the double-Strand break. Trends Cell Biol 26(1):52–64CrossRefPubMedPubMedCentralGoogle Scholar
  20. Cha MY, Kim DK, Mook-Jung I (2015) The role of mitochondrial DNA mutation on neurodegenerative diseases. Exp Mol Med 47:e150CrossRefPubMedPubMedCentralGoogle Scholar
  21. Chen L, Chen JY, Huang YJ, Gu Y, Qiu J, Qian H, Shao C, Zhang X, Hu J, Li H, He S, Zhou Y, Abdel-Wahab O, Zhang DE, Fu XD (2018) The augmented R-loop is a unifying mechanism for Myelodysplastic syndromes induced by high-risk splicing factor mutations. Mol Cell 69(3):412–425CrossRefPubMedPubMedCentralGoogle Scholar
  22. Chitiprolu M, Jagow C, Tremblay V, Bondy-Chorney E, Paris G, Savard A et al (2018) A complex of C9ORF72 and p62 uses arginine methylation to eliminate stress granules by autophagy. Nature Communications 9(1):2794CrossRefPubMedPubMedCentralGoogle Scholar
  23. Cho HS, Shimazu T, Toyokawa G, Daigo Y, Maehara Y, Hayami S et al (2012) Enhanced HSP70 lysine methylation promotes proliferation of cancer cells through activation of Aurora kinase B. Nat Commun 3:1072CrossRefPubMedPubMedCentralGoogle Scholar
  24. Chuikov S, Kurash JK, Wilson JR, Xiao B, Justin N, Ivanov GS et al (2004) Regulation of p53 activity through lysine methylation. Nature 432(7015):353–360CrossRefPubMedPubMedCentralGoogle Scholar
  25. Ciccia A, Elledge SJ (2010) The DNA damage response: making it safe to play with knives. Mol Cell 40(2):179–204CrossRefPubMedPubMedCentralGoogle Scholar
  26. Clarke TL, Sanchez-Bailon MP, Chiang K, Reynolds JJ, Herrero-Ruiz J, Bandeiras TM, Matias PM, Maslen SL, Skehel JM, Stewart GS, Davies CC (2017) PRMT5-dependent methylation of the TIP60 coactivator RUVBL1 is a key regulator of homologous recombination. Mol Cell 65(5):900–916CrossRefPubMedPubMedCentralGoogle Scholar
  27. Coppede F (2011) An overview of DNA repair in amyotrophic lateral sclerosis. Sci World J 11:1679–1691CrossRefGoogle Scholar
  28. Crowe SL, Movsesyan VA, Jorgensen TJ, Kondratyev A (2006) Rapid phosphorylation of histone H2A.X following ionotropic glutamate receptor activation. Eur J Neurosci 23(9):2351–2361CrossRefPubMedPubMedCentralGoogle Scholar
  29. Cuella-Martin R, Oliveira C, Lockstone HE, Snellenberg S, Grolmusova N, Chapman JR (2016) 53BP1 integrates DNA repair and p53-dependent cell fate decisions via distinct mechanisms. Mol Cell 64(1):51–64CrossRefPubMedPubMedCentralGoogle Scholar
  30. Dabin J, Fortuny A, Polo SE (2016) Epigenome maintenance in response to DNA damage. Mol Cell 62(5):712–727CrossRefPubMedPubMedCentralGoogle Scholar
  31. Dantuma NP, van Attikum H (2016) Spatiotemporal regulation of posttranslational modifications in the DNA damage response. EMBO J 35(1):6–23CrossRefGoogle Scholar
  32. Date H, Onodera O, Tanaka H, Iwabuchi K, Uekawa K, Igarashi S, Koike R, Hiroi T, Yuasa T, Awaya Y, Sakai T, Takahashi T, Nagatomo H, Sekijima Y, Kawachi I, Takiyama Y, Nishizawa M, Fukuhara N, Saito K, Sugano S, Tsuji S (2001) Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene. Nat Genet 29(2):184–188CrossRefGoogle Scholar
  33. de Souza-Pinto NC, Wilson DM 3rd, Stevnsner TV, Bohr VA (2008) Mitochondrial DNA, base excision repair and neurodegeneration. DNA Repair 7(7):1098–1109CrossRefPubMedPubMedCentralGoogle Scholar
  34. Del Rizzo PA, Trievel RC (2014) Molecular basis for substrate recognition by lysine methyltransferases and demethylases. Biochim Biophys Acta 1839(12):1404–1415CrossRefGoogle Scholar
  35. Desiere F, Deutsch EW, Nesvizhskii AI, Mallick P, King NL, Eng JK, Aderem A, Boyle R, Brunner E, Donohoe S, Fausto N, Hafen E, Hood L, Katze MG, Kennedy KA, Kregenow F, Lee H, Lin B, Martin D, Ranish JA, Rawlings DJ, Samelson LE, Shiio Y, Watts JD, Wollscheid B, Wright ME, Yan W, Yang L, Yi EC, Zhang H, Aebersold R (2005) Integration with the human genome of peptide sequences obtained by high-throughput mass spectrometry. Genome Biol 6(1):R9CrossRefGoogle Scholar
  36. Dhar S, Gursoy-Yuzugullu O, Parasuram R, Price BD (2017) The tale of a tail: histone H4 acetylation and the repair of DNA breaks. Philos Trans R Soc Lond Ser B Biol Sci 372(1731)Google Scholar
  37. Falnes PO, Jakobsson ME, Davydova E, Ho A, Malecki J (2016) Protein lysine methylation by seven-beta-strand methyltransferases. Biochem J 473(14):1995–2009CrossRefPubMedPubMedCentralGoogle Scholar
  38. Feng J, Dang Y, Zhang W, Zhao X, Zhang C, Hou Z et al (2019) PTEN arginine methylation by PRMT6 suppresses PI3K-AKT signaling and modulates pre-mRNA splicing. Proc Natl Acad Sci U S A 116(14):6868–6877CrossRefPubMedPubMedCentralGoogle Scholar
  39. Fischle W, Tseng BS, Dormann HL, Ueberheide BM, Garcia BA, Shabanowitz J, Hunt DF, Funabiki H, Allis CD (2005) Regulation of HP1-chromatin binding by histone H3 methylation and phosphorylation. Nature 438(7071):1116–1122CrossRefPubMedPubMedCentralGoogle Scholar
  40. Gamper AM, Qiao X, Kim J, Zhang L, DeSimone MC, Rathmell WK, Wan Y (2012) Regulation of KLF4 turnover reveals an unexpected tissue-specific role of pVHL in tumorigenesis. Mol Cell 45(2):233–243CrossRefPubMedPubMedCentralGoogle Scholar
  41. Geoghegan V, Guo A, Trudgian D, Thomas B, Acuto O (2015) Comprehensive identification of arginine methylation in primary T cells reveals regulatory roles in cell signalling. Nat Commun 6:6758CrossRefPubMedPubMedCentralGoogle Scholar
  42. Gong F, Miller KM (2019) Histone methylation and the DNA damage response. Mutat Res 780:37–47CrossRefGoogle Scholar
  43. Groh M, Silva LM, Gromak N (2014) Mechanisms of transcriptional dysregulation in repeat expansion disorders. Biochem Soc Trans 42(4):1123–1128CrossRefGoogle Scholar
  44. Guendel I, Carpio L, Pedati C, Schwartz A, Teal C, Kashanchi F, Kehn-Hall K (2010) Methylation of the tumor suppressor protein, BRCA1, influences its transcriptional cofactor function. PLoS One 5(6):e11379CrossRefPubMedPubMedCentralGoogle Scholar
  45. Guerrero EN, Mitra J, Wang H, Rangaswamy S, Hegde PM, Basu P et al (2019) Amyotrophic lateral sclerosis-associated TDP-43 mutation Q331K prevents nuclear translocation of XRCC4-DNA ligase 4 complex and is linked to genome damage-mediated neuronal apoptosis. Hum Mol Genet.  https://doi.org/10.1093/hmg/ddz062
  46. Guo A, Gu H, Zhou J, Mulhern D, Wang Y, Lee KA, Yang V, Aguiar M, Kornhauser J, Jia X, Ren J, Beausoleil SA, Silva JC, Vemulapalli V, Bedford MT, Comb MJ (2014) Immunoaffinity enrichment and mass spectrometry analysis of protein methylation. Mol Cell Proteomics 13(1):372–387CrossRefGoogle Scholar
  47. Guo J, Dai X, Laurent B, Zheng N, Gan W, Zhang J, Guo A, Yuan M, Liu P, Asara JM, Toker A, Shi Y, Pandolfi PP, Wei W (2019) AKT methylation by SETDB1 promotes AKT kinase activity and oncogenic functions. Nat Cell Biol 21(2):226–237CrossRefPubMedPubMedCentralGoogle Scholar
  48. Guo Z, Zheng L, Xu H, Dai H, Zhou M, Pascua MR, Chen QM, Shen B (2010) Methylation of FEN1 suppresses nearby phosphorylation and facilitates PCNA binding. Nat Chem Biol 6(10):766–773CrossRefPubMedPubMedCentralGoogle Scholar
  49. Gurunathan G, Yu Z, Coulombe Y, Masson JY, Richard S (2015) Arginine methylation of hnRNPUL1 regulates interaction with NBS1 and recruitment to sites of DNA damage. Sci Rep 5:10475CrossRefPubMedPubMedCentralGoogle Scholar
  50. Haeusler AR, Donnelly CJ, Periz G, Simko EA, Shaw PG, Kim MS, Maragakis NJ, Troncoso JC, Pandey A, Sattler R, Rothstein JD, Wang J (2014) C9orf72 nucleotide repeat structures initiate molecular cascades of disease. Nature 507(7491):195–200CrossRefPubMedPubMedCentralGoogle Scholar
  51. Haghandish N, Baldwin RM, Morettin A, Dawit HT, Adhikary H, Masson JY, Mazroui R, Trinkle-Mulcahy L, Côté J (2019) PRMT7 methylates eukaryotic translation initiation factor 2alpha and regulates its role in stress granule formation. Mol Biol Cell 30(6):778–793CrossRefPubMedPubMedCentralGoogle Scholar
  52. Hahm JY, Kim JY, Park JW, Kang JY, Kim KB, Kim SR, Cho H (2019) Methylation of UHRF1 by SET7 is essential for DNA double-strand break repair. Nucleic Acids Res 47(1):184–196CrossRefPubMedPubMedCentralGoogle Scholar
  53. Hamamoto R, Saloura V, Nakamura Y (2015) Critical roles of non-histone protein lysine methylation in human tumorigenesis. Nat Rev Cancer 15(2):110–124CrossRefPubMedPubMedCentralGoogle Scholar
  54. Hamamoto R, Toyokawa G, Nakakido M, Ueda K, Nakamura Y (2014) SMYD2-dependent HSP90 methylation promotes cancer cell proliferation by regulating the chaperone complex formation. Cancer Lett 351(1):126–133CrossRefPubMedPubMedCentralGoogle Scholar
  55. Harper JW, Elledge SJ (2007) The DNA damage response: ten years after. Mol Cell 28(5):739–745CrossRefPubMedPubMedCentralGoogle Scholar
  56. Hashimoto S, Anai H, Hanada K (2016) Mechanisms of interstrand DNA crosslink repair and human disorders. Genes Environ 38:9CrossRefPubMedPubMedCentralGoogle Scholar
  57. He W, Ma X, Yang X, Zhao Y, Qiu J, Hang H (2011) A role for the arginine methylation of Rad9 in checkpoint control and cellular sensitivity to DNA damage. Nucleic Acids Res 39(11):4719–4727CrossRefPubMedPubMedCentralGoogle Scholar
  58. Hegde ML, Bohr VA, Mitra S (2017) DNA damage responses in central nervous system and age-associated neurodegeneration. Mech Ageing Dev 161(Pt A):1–3CrossRefPubMedPubMedCentralGoogle Scholar
  59. Hoch NC, Hanzlikova H, Rulten SL, Tetreault M, Komulainen E, Ju L et al (2017) XRCC1 mutation is associated with PARP1 hyperactivation and cerebellar ataxia. Nature 541(7635):87–91CrossRefGoogle Scholar
  60. Hornbeck PV, Kornhauser JM, Tkachev S, Zhang B, Skrzypek E, Murray B, Latham V, Sullivan M (2012) PhosphoSitePlus: a comprehensive resource for investigating the structure and function of experimentally determined post-translational modifications in man and mouse. Nucleic Acids Res 40(Database issue):D261–D270CrossRefPubMedPubMedCentralGoogle Scholar
  61. Horvath S, Langfelder P, Kwak S, Aaronson J, Rosinski J, Vogt TF, Eszes M, Faull RL, Curtis MA, Waldvogel HJ, Choi OW, Tung S, Vinters HV, Coppola G, Yang XW (2016) Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels. Aging 8(7):1485–1512CrossRefPubMedPubMedCentralGoogle Scholar
  62. Hu D, Gur M, Zhou Z, Gamper A, Hung MC, Fujita N et al (2015) Interplay between arginine methylation and ubiquitylation regulates KLF4-mediated genome stability and carcinogenesis. Nat Commun 6:8419CrossRefPubMedPubMedCentralGoogle Scholar
  63. Huang C, Chen Y, Dai H, Zhang H, Xie M, Zhang H, Chen F, Kang X, Bai X, Chen Z (2019) UBAP2L arginine methylation by PRMT1 modulates stress granule assembly. Cell Death Differ 1–15.  https://doi.org/10.1038/s41418-019-0350-5
  64. Huang J, Dorsey J, Chuikov S, Perez-Burgos L, Zhang X, Jenuwein T et al (2010) G9a and Glp methylate lysine 373 in the tumor suppressor p53. J Biol Chem 285(13):9636–9641CrossRefPubMedPubMedCentralGoogle Scholar
  65. Huang J, Perez-Burgos L, Placek BJ, Sengupta R, Richter M, Dorsey JA, Kubicek S, Opravil S, Jenuwein T, Berger SL (2006) Repression of p53 activity by Smyd2-mediated methylation. Nature 444(7119):629–632CrossRefPubMedPubMedCentralGoogle Scholar
  66. Huang L, Wang Z, Narayanan N, Yang Y (2018) Arginine methylation of the C-terminus RGG motif promotes TOP3B topoisomerase activity and stress granule localization. Nucleic Acids Res 46(6):3061–3074CrossRefPubMedPubMedCentralGoogle Scholar
  67. Jackson SP, Bartek J (2009) The DNA-damage response in human biology and disease. Nature 461(7267):1071–1078CrossRefPubMedPubMedCentralGoogle Scholar
  68. Jackson SP, Durocher D (2013) Regulation of DNA damage responses by ubiquitin and SUMO. Mol Cell 49(5):795–807CrossRefPubMedPubMedCentralGoogle Scholar
  69. Jakobsson ME, Moen A, Bousset L, Egge-Jacobsen W, Kernstock S, Melki R, Falnes PØ (2013) Identification and characterization of a novel human methyltransferase modulating Hsp70 protein function through lysine methylation. J Biol Chem 288(39):27752–27763CrossRefPubMedPubMedCentralGoogle Scholar
  70. Jiang Y, Trescott L, Holcomb J, Zhang X, Brunzelle J, Sirinupong N, Shi X, Yang Z (2014) Structural insights into estrogen receptor alpha methylation by histone methyltransferase SMYD2, a cellular event implicated in estrogen signaling regulation. J Mol Biol 426(20):3413–3425CrossRefPubMedPubMedCentralGoogle Scholar
  71. Kassner I, Andersson A, Fey M, Tomas M, Ferrando-May E, Hottiger MO (2013) SET7/9-dependent methylation of ARTD1 at K508 stimulates poly-ADP-ribose formation after oxidative stress. Open Biol 3(10):120173CrossRefPubMedPubMedCentralGoogle Scholar
  72. Kim JJ, Lee SY, Miller KM (2019) Preserving genome integrity and function: the DNA damage response and histone modifications. Crit Rev Biochem Mol Biol 54(3):208–241CrossRefPubMedPubMedCentralGoogle Scholar
  73. Kogure M, Takawa M, Saloura V, Sone K, Piao L, Ueda K et al (2013) The oncogenic polycomb histone methyltransferase EZH2 methylates lysine 120 on histone H2B and competes ubiquitination. Neoplasia 11:1251–1261CrossRefGoogle Scholar
  74. Kontaki H, Talianidis I (2010) Lysine methylation regulates E2F1-induced cell death. Mol Cell 39(1):152–160CrossRefPubMedPubMedCentralGoogle Scholar
  75. Kraemer KH, Patronas NJ, Schiffmann R, Brooks BP, Tamura D, DiGiovanna JJ (2007) Xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome: a complex genotype-phenotype relationship. Neuroscience 145(4):1388–1396CrossRefPubMedPubMedCentralGoogle Scholar
  76. Kwiatkowski TJ Jr, Bosco DA, Leclerc AL, Tamrazian E, Vanderburg CR, Russ C et al (2009) Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 323(5918):1205–1208CrossRefPubMedPubMedCentralGoogle Scholar
  77. Larsen SC, Sylvestersen KB, Mund A, Lyon D, Mullari M, Madsen MV et al (2016) Proteome-wide analysis of arginine monomethylation reveals widespread occurrence in human cells. Science Signal 9(443):rs9CrossRefGoogle Scholar
  78. Laugel V, Dalloz C, Durand M, Sauvanaud F, Kristensen U, Vincent MC, Pasquier L, Odent S, Cormier-Daire V, Gener B, Tobias ES, Tolmie JL, Martin-Coignard D, Drouin-Garraud V, Heron D, Journel H, Raffo E, Vigneron J, Lyonnet S, Murday V, Gubser-Mercati D, Funalot B, Brueton L, Sanchez del Pozo J, Muñoz E, Gennery AR, Salih M, Noruzinia M, Prescott K, Ramos L, Stark Z, Fieggen K, Chabrol B, Sarda P, Edery P, Bloch-Zupan A, Fawcett H, Pham D, Egly JM, Lehmann AR, Sarasin A, Dollfus H (2010) Mutation update for the CSB/ERCC6 and CSA/ERCC8 genes involved in Cockayne syndrome. Hum Mutat 31(2):113–126CrossRefPubMedPubMedCentralGoogle Scholar
  79. Lee JM, Lee JS, Kim H, Kim K, Park H, Kim JY, Lee SH, Kim IS, Kim J, Lee M, Chung CH, Seo SB, Yoon JB, Ko E, Noh DY, Kim KI, Kim KK, Baek SH (2012) EZH2 generates a methyl degron that is recognized by the DCAF1/DDB1/CUL4 E3 ubiquitin ligase complex. Mol Cell 48(4):572–586CrossRefPubMedPubMedCentralGoogle Scholar
  80. Lee YH, Stallcup MR (2011) Roles of protein arginine methylation in DNA damage signaling pathways is CARM1 a life-or-death decision point? Cell Cycle 10(9):1343–1344CrossRefPubMedPubMedCentralGoogle Scholar
  81. Lieber MR, Ma Y, Pannicke U, Schwarz K (2003) Mechanism and regulation of human non-homologous DNA end-joining. Nat Rev Mol Cell Biol 4(9):712–720CrossRefPubMedPubMedCentralGoogle Scholar
  82. Lieberman HB (2006) Rad9, an evolutionarily conserved gene with multiple functions for preserving genomic integrity. J Cell Biochem 97(4):690–697CrossRefPubMedPubMedCentralGoogle Scholar
  83. Lim YW, Sanz LA, Xu X, Hartono SR, Chedin F (2015) Genome-wide DNA hypomethylation and RNA:DNA hybrid accumulation in Aicardi-Goutieres syndrome. eLife 4.  https://doi.org/10.7554/eLife.08007
  84. Liu H, Galka M, Mori E, Liu X, Lin YF, Wei R, Pittock P, Voss C, Dhami G, Li X, Miyaji M, Lajoie G, Chen B, Li SS (2013) A method for systematic mapping of protein lysine methylation identifies functions for HP1beta in DNA damage response. Mol Cell 50(5):723–735CrossRefPubMedPubMedCentralGoogle Scholar
  85. Liu LM, Sun WZ, Fan XZ, Xu YL, Cheng MB, Zhang Y (2019) Methylation of C/EBPalpha by PRMT1 inhibits its tumor-suppressive function in breast Cancer. Cancer Res 79(11):2865–2877CrossRefPubMedPubMedCentralGoogle Scholar
  86. Liu X, Wang D, Zhao Y, Tu B, Zheng Z, Wang L, Wang H, Gu W, Roeder RG, Zhu WG (2011) Methyltransferase Set7/9 regulates p53 activity by interacting with Sirtuin 1 (SIRT1). Proc Natl Acad Sci U S A 108(5):1925–1930CrossRefPubMedPubMedCentralGoogle Scholar
  87. Loomis EW, Sanz LA, Chedin F, Hagerman PJ (2014) Transcription-associated R-loop formation across the human FMR1 CGG-repeat region. PLoS Genet 10(4):e1004294CrossRefPubMedPubMedCentralGoogle Scholar
  88. Lorton BM, Shechter D (2019) Cellular consequences of arginine methylation. Cell Mol Life Sci 76(15):2933–2956CrossRefPubMedPubMedCentralGoogle Scholar
  89. Lu J, Matunis MJ (2013) A mediator methylation mystery: JMJD1C demethylates MDC1 to regulate DNA repair. Nat Struct Mol Biol 20(12):1346–1348CrossRefPubMedPubMedCentralGoogle Scholar
  90. Lukas J, Lukas C, Bartek J (2011) More than just a focus: the chromatin response to DNA damage and its role in genome integrity maintenance. Nat Cell Biol 13(10):1161–1169CrossRefPubMedPubMedCentralGoogle Scholar
  91. Maiuri T, Mocle AJ, Hung CL, Xia J, van Roon-Mom WM, Truant R (2017) Huntingtin is a scaffolding protein in the ATM oxidative DNA damage response complex. Hum Mol Genet 26(2):395–406PubMedPubMedCentralGoogle Scholar
  92. Malecki J, Ho AY, Moen A, Dahl HA, Falnes PO (2015) Human METTL20 is a mitochondrial lysine methyltransferase that targets the beta subunit of electron transfer flavoprotein (ETFbeta) and modulates its activity. J Biol Chem 290(1):423–434CrossRefPubMedPubMedCentralGoogle Scholar
  93. Malecki JM, Willemen H, Pinto R, Ho AYY, Moen A, Kjonstad IF et al (2019) Lysine methylation by the mitochondrial methyltransferase FAM173B optimizes the function of mitochondrial ATP synthase. J Biol Chem 294(4):1128–1141CrossRefPubMedPubMedCentralGoogle Scholar
  94. Mazur PK, Reynoird N, Khatri P, Jansen PW, Wilkinson AW, Liu S, Barbash O, van Aller G, Huddleston M, Dhanak D, Tummino PJ, Kruger RG, Garcia BA, Butte AJ, Vermeulen M, Sage J, Gozani O (2014) SMYD3 links lysine methylation of MAP3K2 to Ras-driven cancer. Nature 510(7504):283–287CrossRefPubMedPubMedCentralGoogle Scholar
  95. McKinnon PJ (2009) DNA repair deficiency and neurological disease. Nat Rev Neurosci 10(2):100–112CrossRefPubMedPubMedCentralGoogle Scholar
  96. McKinnon PJ (2013) Maintaining genome stability in the nervous system. Nat Neurosci 16(11):1523–1529CrossRefPubMedPubMedCentralGoogle Scholar
  97. Mersaoui SY, Yu Z, Coulombe Y, Karam M, Busatto FF, Masson JY, Richard S (2019) Arginine methylation of the DDX5 helicase RGG/RG motif by PRMT5 regulates resolution of RNA:DNA hybrids. EMBO J 38(15):e100986CrossRefPubMedPubMedCentralGoogle Scholar
  98. Mitra J, Guerrero EN, Hegde PM, Liachko NF, Wang H, Vasquez V et al (2019) Motor neuron disease-associated loss of nuclear TDP-43 is linked to DNA double-strand break repair defects. Proc Natl Acad Sci U S A.  https://doi.org/10.1073/pnas.1818415116
  99. Morales Y, Caceres T, May K, Hevel JM (2016) Biochemistry and regulation of the protein arginine methyltransferases (PRMTs). Arch Biochem Biophys 590:138–152CrossRefPubMedPubMedCentralGoogle Scholar
  100. Moreira MC, Barbot C, Tachi N, Kozuka N, Uchida E, Gibson T, Mendonça P, Costa M, Barros J, Yanagisawa T, Watanabe M, Ikeda Y, Aoki M, Nagata T, Coutinho P, Sequeiros J, Koenig M (2001) The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin. Nat Genet 29(2):189–193CrossRefPubMedPubMedCentralGoogle Scholar
  101. Morris M, Knudsen GM, Maeda S, Trinidad JC, Ioanoviciu A, Burlingame AL, Mucke L (2015) Tau post-translational modifications in wild-type and human amyloid precursor protein transgenic mice. Nat Neurosci 18(8):1183–1189CrossRefGoogle Scholar
  102. Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T, Grossman M, Clark CM, McCluskey L, Miller BL, Masliah E, Mackenzie IR, Feldman H, Feiden W, Kretzschmar HA, Trojanowski JQ, Lee VM (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314(5796):130–133CrossRefPubMedPubMedCentralGoogle Scholar
  103. Nott TJ, Petsalaki E, Farber P, Jervis D, Fussner E, Plochowietz A, Craggs TD, Bazett-Jones DP, Pawson T, Forman-Kay JD, Baldwin AJ (2015) Phase transition of a disordered nuage protein generates environmentally responsive membraneless organelles. Mol Cell 57(5):936–947CrossRefPubMedPubMedCentralGoogle Scholar
  104. O'Driscoll M, Cerosaletti KM, Girard PM, Dai Y, Stumm M, Kysela B et al (2001) Ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency. Mol Cell 8(6):1175–1185CrossRefPubMedPubMedCentralGoogle Scholar
  105. O'Driscoll M, Ruiz-Perez VL, Woods CG, Jeggo PA, Goodship JA (2003) A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome. Nat Genet 33(4):497–501CrossRefPubMedPubMedCentralGoogle Scholar
  106. Pansarasa O, Bordoni M, Diamanti L, Sproviero D, Gagliardi S, Cereda C (2018) SOD1 in amyotrophic lateral sclerosis: "ambivalent" behavior connected to the disease. Int J Mol Sci 19(5):1345CrossRefGoogle Scholar
  107. Peng C, Wong CC (2017) The story of protein arginine methylation: characterization, regulation, and function. Expert Rev Proteomics 14(2):157–170CrossRefPubMedPubMedCentralGoogle Scholar
  108. Perego MGL, Taiana M, Bresolin N, Comi GP, Corti S (2019) R-loops in motor neuron diseases. Mol Neurobiol 56(4):2579–2589CrossRefPubMedPubMedCentralGoogle Scholar
  109. Piao L, Kang D, Suzuki T, Masuda A, Dohmae N, Nakamura Y, Hamamoto R (2014) The histone methyltransferase SMYD2 methylates PARP1 and promotes poly(ADP-ribosyl)ation activity in cancer cells. Neoplasia 16(3):257–264CrossRefPubMedPubMedCentralGoogle Scholar
  110. Poletto M, Yang D, Fletcher SC, Vendrell I, Fischer R, Legrand AJ, Dianov GL (2017) Modulation of proteostasis counteracts oxidative stress and affects DNA base excision repair capacity in ATM-deficient cells. Nucleic Acids Res 45(17):10042–10055CrossRefPubMedPubMedCentralGoogle Scholar
  111. Polo SE, Almouzni G (2015) Chromatin dynamics after DNA damage: the legacy of the access-repair-restore model. DNA Repair (Amst) 36:114–121CrossRefGoogle Scholar
  112. Polo SE, Blackford AN, Chapman JR, Baskcomb L, Gravel S, Rusch A, Thomas A, Blundred R, Smith P, Kzhyshkowska J, Dobner T, Taylor AM, Turnell AS, Stewart GS, Grand RJ, Jackson SP (2012) Regulation of DNA-end resection by hnRNPU-like proteins promotes DNA double-strand break signaling and repair. Mol Cell 45(4):505–516CrossRefPubMedPubMedCentralGoogle Scholar
  113. Polo SE, Jackson SP (2011) Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications. Genes Dev 25(5):409–433CrossRefPubMedPubMedCentralGoogle Scholar
  114. Raschella G, Melino G, Malewicz M (2017) New factors in mammalian DNA repair-the chromatin connection. Oncogene 36(33):4673–4681CrossRefPubMedPubMedCentralGoogle Scholar
  115. Rehman I, Basu SM, Das SK, Bhattacharjee S, Ghosh A, Pommier Y, Das BB (2018) PRMT5-mediated arginine methylation of TDP1 for the repair of topoisomerase I covalent complexes. Nucleic Acids Res 46(11):5601–5617CrossRefPubMedPubMedCentralGoogle Scholar
  116. Rhein VF, Carroll J, Ding S, Fearnley IM, Walker JE (2017) Human METTL12 is a mitochondrial methyltransferase that modifies citrate synthase. FEBS Lett 591(12):1641–1652CrossRefPubMedPubMedCentralGoogle Scholar
  117. Rothbart SB, Krajewski K, Nady N, Tempel W, Xue S, Badeaux AI, Barsyte-Lovejoy D, Martinez JY, Bedford MT, Fuchs SM, Arrowsmith CH, Strahl BD (2012) Association of UHRF1 with methylated H3K9 directs the maintenance of DNA methylation. Nat Struct Mol Biol 19(11):1155–1160CrossRefPubMedPubMedCentralGoogle Scholar
  118. Saddic LA, West LE, Aslanian A, Yates JR 3rd, Rubin SM, Gozani O et al (2010) Methylation of the retinoblastoma tumor suppressor by SMYD2. J Biol Chem 285(48):37733–37740CrossRefPubMedPubMedCentralGoogle Scholar
  119. Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle DA, Smith S, Uziel T, Sfez S, Ashkenazi M, Pecker I, Frydman M, Harnik R, Patanjali SR, Simmons A, Clines GA, Sartiel A, Gatti RA, Chessa L, Sanal O, Lavin MF, Jaspers NG, Taylor AM, Arlett CF, Miki T, Weissman SM, Lovett M, Collins FS, Shiloh Y (1995) A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 268(5218):1749–1753CrossRefPubMedPubMedCentralGoogle Scholar
  120. Shen C, Wang D, Liu X, Gu B, Du Y, Wei FZ et al (2015) SET7/9 regulates cancer cell proliferation by influencing beta-catenin stability. FASEB J 29(10):4313–4323CrossRefPubMedPubMedCentralGoogle Scholar
  121. Shi X, Kachirskaia I, Yamaguchi H, West LE, Wen H, Wang EW, Dutta S, Appella E, Gozani O (2007) Modulation of p53 function by SET8-mediated methylation at lysine 382. Mol Cell 27(4):636–646CrossRefPubMedPubMedCentralGoogle Scholar
  122. Shi YG, Tsukada Y (2013) The discovery of histone demethylases. Cold Spring Harb Perspect Biol 5(9):a017947CrossRefPubMedPubMedCentralGoogle Scholar
  123. Silva S, Camino LP, Aguilera A (2018) Human mitochondrial degradosome prevents harmful mitochondrial R loops and mitochondrial genome instability. Proc Natl Acad Sci U S A 115(43):11024–11029CrossRefPubMedPubMedCentralGoogle Scholar
  124. Skourti-Stathaki K, Proudfoot NJ, Gromak N (2011) Human senataxin resolves RNA/DNA hybrids formed at transcriptional pause sites to promote Xrn2-dependent termination. Mol Cell 42(6):794–805CrossRefPubMedPubMedCentralGoogle Scholar
  125. Soria G, Polo SE, Almouzni G (2012) Prime, repair, restore: the active role of chromatin in the DNA damage response. Mol Cell 46(6):722–734CrossRefPubMedPubMedCentralGoogle Scholar
  126. Stewart GS, Maser RS, Stankovic T, Bressan DA, Kaplan MI, Jaspers NG, Raams A, Byrd PJ, Petrini JH, Taylor AM (1999) The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder. Cell 99(6):577–587CrossRefPubMedPubMedCentralGoogle Scholar
  127. Stirling PC, Chan YA, Minaker SW, Aristizabal MJ, Barrett I, Sipahimalani P, Kobor MS, Hieter P (2012) R-loop-mediated genome instability in mRNA cleavage and polyadenylation mutants. Genes Dev 26(2):163–175CrossRefPubMedPubMedCentralGoogle Scholar
  128. Subramanian K, Jia D, Kapoor-Vazirani P, Powell DR, Collins RE, Sharma D, Peng J, Cheng X, Vertino PM (2008) Regulation of estrogen receptor alpha by the SET7 lysine methyltransferase. Mol Cell 30(3):336–347CrossRefPubMedPubMedCentralGoogle Scholar
  129. Takashima H, Boerkoel CF, John J, Saifi GM, Salih MA, Armstrong D, Mao Y, Quiocho FA, Roa BB, Nakagawa M, Stockton DW, Lupski JR (2002) Mutation of TDP1, encoding a topoisomerase I-dependent DNA damage repair enzyme, in spinocerebellar ataxia with axonal neuropathy. Nat Genet 32(2):267–272CrossRefPubMedPubMedCentralGoogle Scholar
  130. Takawa M, Cho HS, Hayami S, Toyokawa G, Kogure M, Yamane Y, Iwai Y, Maejima K, Ueda K, Masuda A, Dohmae N, Field HI, Tsunoda T, Kobayashi T, Akasu T, Sugiyama M, Ohnuma S, Atomi Y, Ponder BA, Nakamura Y, Hamamoto R (2012) Histone lysine methyltransferase SETD8 promotes carcinogenesis by deregulating PCNA expression. Cancer Res 72(13):3217–3227CrossRefPubMedPubMedCentralGoogle Scholar
  131. Thomas SN, Funk KE, Wan Y, Liao Z, Davies P, Kuret J, Yang AJ (2012) Dual modification of Alzheimer's disease PHF-tau protein by lysine methylation and ubiquitylation: a mass spectrometry approach. Acta Neuropathol 123(1):105–117CrossRefPubMedPubMedCentralGoogle Scholar
  132. Thomas SN, Yang AJ (2017) Mass spectrometry analysis of lysine posttranslational modifications of tau protein from Alzheimer’s disease brain. Methods Mol Biol 1523:161–177CrossRefPubMedPubMedCentralGoogle Scholar
  133. van der Horst A, Burgering BM (2007) Stressing the role of FoxO proteins in lifespan and disease. Nat Rev Mol Cell Biol 8(6):440–450CrossRefPubMedPubMedCentralGoogle Scholar
  134. Vance C, Rogelj B, Hortobagyi T, De Vos KJ, Nishimura AL, Sreedharan J et al (2009) Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323(5918):1208–1211CrossRefPubMedPubMedCentralGoogle Scholar
  135. Varon R, Vissinga C, Platzer M, Cerosaletti KM, Chrzanowska KH, Saar K, Beckmann G, Seemanová E, Cooper PR, Nowak NJ, Stumm M, Weemaes CM, Gatti RA, Wilson RK, Digweed M, Rosenthal A, Sperling K, Concannon P, Reis A (1998) Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell 93(3):467–476CrossRefPubMedPubMedCentralGoogle Scholar
  136. Wahba L, Amon JD, Koshland D, Vuica-Ross M (2011) RNase H and multiple RNA biogenesis factors cooperate to prevent RNA:DNA hybrids from generating genome instability. Mol Cell 44(6):978–988CrossRefPubMedPubMedCentralGoogle Scholar
  137. Wang D, Zhou J, Liu X, Lu D, Shen C, Du Y et al (2013a) Methylation of SUV39H1 by SET7/9 results in heterochromatin relaxation and genome instability. Proc Natl Acad Sci U S A 110(14):5516–5521CrossRefPubMedPubMedCentralGoogle Scholar
  138. Wang G, Long J, Gao Y, Zhang W, Han F, Xu C, Sun L, Yang SC, Lan J, Hou Z, Cai Z, Jin G, Hsu CC, Wang YH, Hu J, Chen TY, Li H, Lee MG, Lin HK (2019) SETDB1-mediated methylation of Akt promotes its K63-linked ubiquitination and activation leading to tumorigenesis. Nat Cell Biol 21(2):214–225CrossRefPubMedPubMedCentralGoogle Scholar
  139. Wang H, Guo W, Mitra J, Hegde PM, Vandoorne T, Eckelmann BJ, Mitra S, Tomkinson AE, van den Bosch L, Hegde ML (2018) Mutant FUS causes DNA ligation defects to inhibit oxidative damage repair in amyotrophic lateral sclerosis. Nat Commun 9(1):3683CrossRefPubMedPubMedCentralGoogle Scholar
  140. Wang H, Hegde ML (2019) New mechanisms of DNA repair defects in fused in sarcoma-associated Neurodegeneration: stage set for DNA repair-based therapeutics? J Exp Neurosci 13.  https://doi.org/10.1177/1179069519856358
  141. Wang JQ, Chen Q, Wang X, Wang QC, Wang Y, Cheng HP, Guo C, Sun Q, Chen Q, Tang TS (2013b) Dysregulation of mitochondrial calcium signaling and superoxide flashes cause mitochondrial genomic DNA damage in Huntington disease. J Biol Chem 288(5):3070–3084CrossRefGoogle Scholar
  142. Watanabe S, Watanabe K, Akimov V, Bartkova J, Blagoev B, Lukas J, Bartek J (2013) JMJD1C demethylates MDC1 to regulate the RNF8 and BRCA1-mediated chromatin response to DNA breaks. Nat Struct Mol Biol 20(12):1425–1433CrossRefPubMedPubMedCentralGoogle Scholar
  143. Whetstine JR, Nottke A, Lan F, Huarte M, Smolikov S, Chen Z et al (2006) Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell 125(3):467–481CrossRefPubMedPubMedCentralGoogle Scholar
  144. Woodbine L, Neal JA, Sasi NK, Shimada M, Deem K, Coleman H, Dobyns WB, Ogi T, Meek K, Davies EG, Jeggo PA (2013) PRKDC mutations in a SCID patient with profound neurological abnormalities. J Clin Invest 123(7):2969–2980CrossRefPubMedPubMedCentralGoogle Scholar
  145. Xie Q, Bai Y, Wu J, Sun Y, Wang Y, Zhang Y, Mei P, Yuan Z (2011) Methylation-mediated regulation of E2F1 in DNA damage-induced cell death. J Recept Signal Transduct Res 31(2):139–146CrossRefPubMedPubMedCentralGoogle Scholar
  146. Xie Q, Hao Y, Tao L, Peng S, Rao C, Chen H et al (2012) Lysine methylation of FOXO3 regulates oxidative stress-induced neuronal cell death. EMBO Rep 13(4):371–377CrossRefPubMedPubMedCentralGoogle Scholar
  147. Xiong YS, Liu FF, Liu D, Huang HZ, Wei N, Tan L, Chen JG, Man HY, Gong CX, Lu Y, Wang JZ, Zhu LQ (2015) Opposite effects of two estrogen receptors on tau phosphorylation through disparate effects on the miR-218/PTPA pathway. Aging Cell 14(5):867–877CrossRefPubMedPubMedCentralGoogle Scholar
  148. Yamagata K, Daitoku H, Takahashi Y, Namiki K, Hisatake K, Kako K, Mukai H, Kasuya Y, Fukamizu A (2008) Arginine methylation of FOXO transcription factors inhibits their phosphorylation by Akt. Mol Cell 32(2):221–231CrossRefPubMedPubMedCentralGoogle Scholar
  149. Yamaguchi A, Kitajo K (2012) The effect of PRMT1-mediated arginine methylation on the subcellular localization, stress granules, and detergent-insoluble aggregates of FUS/TLS. PLoS One 7(11):e49267CrossRefPubMedPubMedCentralGoogle Scholar
  150. Yang Y, McBride KM, Hensley S, Lu Y, Chedin F, Bedford MT (2014) Arginine methylation facilitates the recruitment of TOP3B to chromatin to prevent R loop accumulation. Mol Cell 53(3):484–497CrossRefPubMedPubMedCentralGoogle Scholar
  151. Yu Z, Vogel G, Coulombe Y, Dubeau D, Spehalski E, Hebert J et al (2012) The MRE11 GAR motif regulates DNA double-strand break processing and ATR activation. Cell Res 22(2):305–320CrossRefPubMedPubMedCentralGoogle Scholar
  152. Zhang M, Xu JY, Hu H, Ye BC, Tan M (2018) Systematic proteomic analysis of protein methylation in prokaryotes and eukaryotes revealed distinct substrate specificity. Proteomics 18(1):1700300CrossRefGoogle Scholar
  153. Zhang X, Peng D, Xi Y, Yuan C, Sagum CA, Klein BJ et al (2016) G9a-mediated methylation of ERalpha links the PHF20/MOF histone acetyltransferase complex to hormonal gene expression. Nat Commun 7:10810CrossRefPubMedPubMedCentralGoogle Scholar
  154. Zinovkina LA (2018) Mechanisms of mitochondrial DNA repair in mammals. Biochemistry (Mosc) 83(3):233–249CrossRefGoogle Scholar

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© The International CCN Society 2019

Authors and Affiliations

  1. 1.Department of BiochemistrySree Chitra Tirunal Institute for Medical Sciences and TechnologyThiruvananthapuramIndia
  2. 2.Rajiv Gandhi Cancer Institute and Research CentreNew DelhiIndia

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