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

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Journal of Cell Communication and Signaling Aims and scope

A Correction to this article was published on 29 September 2020

This article has been updated

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.

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Change history

  • 29 September 2020

    The original version of this article unfortunately requires correction where the name of a methyltransferase was represented wrongly.

Abbreviations

53BP1:

p53 binding protein

Aβ:

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

References

  • 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):731–734

    CAS  PubMed  Google Scholar 

  • Aguilera A, Garcia-Muse T (2012) R loops: from transcription byproducts to threats to genome stability. Mol Cell 46(2):115–124

    CAS  PubMed  Google Scholar 

  • 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):1428–1436

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):835–846

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):353–363

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):515–517

    CAS  PubMed  Google Scholar 

  • Bicker KL, Thompson PR (2013) The protein arginine deiminases: structure, function, inhibition, and disease. Biopolymers 99(2):155–163

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):671–676

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):1834–1841

    CAS  PubMed  Google Scholar 

  • 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):12543–12553

    CAS  PubMed  PubMed Central  Google Scholar 

  • Branzei D, Foiani M (2008) Regulation of DNA repair throughout the cell cycle. Nat Rev Mol Cell Biol 9(4):297–308

    CAS  PubMed  Google Scholar 

  • Branzei D, Szakal B (2016) DNA damage tolerance by recombination: molecular pathways and DNA structures. DNA Repair 44:68–75

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):474–479

    CAS  PubMed  PubMed Central  Google Scholar 

  • Brinkmann K, Schell M, Hoppe T, Kashkar H (2015) Regulation of the DNA damage response by ubiquitin conjugation. Front Genet 6:98

    PubMed  PubMed Central  Google Scholar 

  • 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):305–310

    CAS  PubMed  Google Scholar 

  • 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):227–240

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):477–486

    CAS  PubMed  Google Scholar 

  • 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):11341–11346

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ceccaldi R, Rondinelli B, D'Andrea AD (2016) Repair pathway choices and consequences at the double-Strand break. Trends Cell Biol 26(1):52–64

    CAS  PubMed  Google Scholar 

  • Cha MY, Kim DK, Mook-Jung I (2015) The role of mitochondrial DNA mutation on neurodegenerative diseases. Exp Mol Med 47:e150

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):412–425

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):2794

    PubMed  PubMed Central  Google Scholar 

  • 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 3:1072

    PubMed  Google Scholar 

  • 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):353–360

    CAS  PubMed  Google Scholar 

  • Ciccia A, Elledge SJ (2010) The DNA damage response: making it safe to play with knives. Mol Cell 40(2):179–204

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):900–916

    CAS  PubMed  PubMed Central  Google Scholar 

  • Coppede F (2011) An overview of DNA repair in amyotrophic lateral sclerosis. Sci World J 11:1679–1691

    CAS  Google Scholar 

  • 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):2351–2361

    PubMed  PubMed Central  Google Scholar 

  • 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):51–64

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dabin J, Fortuny A, Polo SE (2016) Epigenome maintenance in response to DNA damage. Mol Cell 62(5):712–727

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dantuma NP, van Attikum H (2016) Spatiotemporal regulation of posttranslational modifications in the DNA damage response. EMBO J 35(1):6–23

    CAS  PubMed  Google Scholar 

  • 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):184–188

    CAS  PubMed  Google Scholar 

  • de Souza-Pinto NC, Wilson DM 3rd, Stevnsner TV, Bohr VA (2008) Mitochondrial DNA, base excision repair and neurodegeneration. DNA Repair 7(7):1098–1109

    PubMed  PubMed Central  Google Scholar 

  • Del Rizzo PA, Trievel RC (2014) Molecular basis for substrate recognition by lysine methyltransferases and demethylases. Biochim Biophys Acta 1839(12):1404–1415

    PubMed  Google Scholar 

  • 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):R9

    PubMed  Google Scholar 

  • 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)

  • Falnes PO, Jakobsson ME, Davydova E, Ho A, Malecki J (2016) Protein lysine methylation by seven-beta-strand methyltransferases. Biochem J 473(14):1995–2009

    CAS  PubMed  Google Scholar 

  • 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):6868–6877

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):1116–1122

    CAS  PubMed  Google Scholar 

  • 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):233–243

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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 6:6758

    CAS  PubMed  Google Scholar 

  • Gong F, Miller KM (2019) Histone methylation and the DNA damage response. Mutat Res 780:37–47

    CAS  Google Scholar 

  • Groh M, Silva LM, Gromak N (2014) Mechanisms of transcriptional dysregulation in repeat expansion disorders. Biochem Soc Trans 42(4):1123–1128

    CAS  PubMed  Google Scholar 

  • 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):e11379

    PubMed  PubMed Central  Google Scholar 

  • 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

  • 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):372–387

    CAS  PubMed  Google Scholar 

  • 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):226–237

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):766–773

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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 5:10475

    PubMed  PubMed Central  Google Scholar 

  • 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):195–200

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):778–793

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):184–196

    CAS  PubMed  Google Scholar 

  • Hamamoto R, Saloura V, Nakamura Y (2015) Critical roles of non-histone protein lysine methylation in human tumorigenesis. Nat Rev Cancer 15(2):110–124

    CAS  PubMed  Google Scholar 

  • 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):126–133

    CAS  PubMed  Google Scholar 

  • Harper JW, Elledge SJ (2007) The DNA damage response: ten years after. Mol Cell 28(5):739–745

    CAS  PubMed  Google Scholar 

  • Hashimoto S, Anai H, Hanada K (2016) Mechanisms of interstrand DNA crosslink repair and human disorders. Genes Environ 38:9

    PubMed  PubMed Central  Google Scholar 

  • 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):4719–4727

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hegde ML, Bohr VA, Mitra S (2017) DNA damage responses in central nervous system and age-associated neurodegeneration. Mech Ageing Dev 161(Pt A):1–3

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):87–91

    CAS  PubMed  Google Scholar 

  • 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–D270

    CAS  PubMed  Google Scholar 

  • 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):1485–1512

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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 6:8419

    CAS  PubMed  Google Scholar 

  • 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

  • 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):9636–9641

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):629–632

    CAS  PubMed  Google Scholar 

  • 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):3061–3074

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jackson SP, Bartek J (2009) The DNA-damage response in human biology and disease. Nature 461(7267):1071–1078

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jackson SP, Durocher D (2013) Regulation of DNA damage responses by ubiquitin and SUMO. Mol Cell 49(5):795–807

    CAS  PubMed  Google Scholar 

  • 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):27752–27763

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):3413–3425

    CAS  PubMed  Google Scholar 

  • 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):120173

    PubMed  PubMed Central  Google Scholar 

  • 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):208–241

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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 11:1251–1261

    Google Scholar 

  • Kontaki H, Talianidis I (2010) Lysine methylation regulates E2F1-induced cell death. Mol Cell 39(1):152–160

    CAS  PubMed  Google Scholar 

  • 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):1388–1396

    CAS  PubMed  Google Scholar 

  • 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):1205–1208

    CAS  PubMed  Google Scholar 

  • 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):rs9

    Google Scholar 

  • 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):113–126

    CAS  PubMed  Google Scholar 

  • 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):572–586

    CAS  PubMed  Google Scholar 

  • 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):1343–1344

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):712–720

    CAS  PubMed  Google Scholar 

  • Lieberman HB (2006) Rad9, an evolutionarily conserved gene with multiple functions for preserving genomic integrity. J Cell Biochem 97(4):690–697

    CAS  PubMed  Google Scholar 

  • 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

  • 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):723–735

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):2865–2877

    CAS  PubMed  Google Scholar 

  • 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):1925–1930

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):e1004294

    PubMed  PubMed Central  Google Scholar 

  • Lorton BM, Shechter D (2019) Cellular consequences of arginine methylation. Cell Mol Life Sci 76(15):2933–2956

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lu J, Matunis MJ (2013) A mediator methylation mystery: JMJD1C demethylates MDC1 to regulate DNA repair. Nat Struct Mol Biol 20(12):1346–1348

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):1161–1169

    CAS  PubMed  Google Scholar 

  • 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):395–406

    CAS  PubMed  Google Scholar 

  • 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):423–434

    CAS  PubMed  Google Scholar 

  • 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):1128–1141

    CAS  PubMed  Google Scholar 

  • 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):283–287

    CAS  PubMed  PubMed Central  Google Scholar 

  • McKinnon PJ (2009) DNA repair deficiency and neurological disease. Nat Rev Neurosci 10(2):100–112

    CAS  PubMed  PubMed Central  Google Scholar 

  • McKinnon PJ (2013) Maintaining genome stability in the nervous system. Nat Neurosci 16(11):1523–1529

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):e100986

    PubMed  PubMed Central  Google Scholar 

  • 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

  • Morales Y, Caceres T, May K, Hevel JM (2016) Biochemistry and regulation of the protein arginine methyltransferases (PRMTs). Arch Biochem Biophys 590:138–152

    CAS  PubMed  Google Scholar 

  • 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):189–193

    CAS  PubMed  Google Scholar 

  • 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):1183–1189

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):130–133

    CAS  PubMed  Google Scholar 

  • 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):936–947

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):1175–1185

    CAS  PubMed  Google Scholar 

  • 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):497–501

    CAS  PubMed  Google Scholar 

  • 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):1345

    PubMed Central  Google Scholar 

  • Peng C, Wong CC (2017) The story of protein arginine methylation: characterization, regulation, and function. Expert Rev Proteomics 14(2):157–170

    CAS  PubMed  Google Scholar 

  • Perego MGL, Taiana M, Bresolin N, Comi GP, Corti S (2019) R-loops in motor neuron diseases. Mol Neurobiol 56(4):2579–2589

    CAS  PubMed  Google Scholar 

  • 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):257–264

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):10042–10055

    CAS  PubMed  PubMed Central  Google Scholar 

  • Polo SE, Almouzni G (2015) Chromatin dynamics after DNA damage: the legacy of the access-repair-restore model. DNA Repair (Amst) 36:114–121

    CAS  Google Scholar 

  • 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):505–516

    CAS  PubMed  PubMed Central  Google Scholar 

  • Polo SE, Jackson SP (2011) Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications. Genes Dev 25(5):409–433

    CAS  PubMed  PubMed Central  Google Scholar 

  • Raschella G, Melino G, Malewicz M (2017) New factors in mammalian DNA repair-the chromatin connection. Oncogene 36(33):4673–4681

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):5601–5617

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):1641–1652

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):1155–1160

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):37733–37740

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):1749–1753

    CAS  PubMed  Google Scholar 

  • 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):4313–4323

    CAS  PubMed  Google Scholar 

  • 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):636–646

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shi YG, Tsukada Y (2013) The discovery of histone demethylases. Cold Spring Harb Perspect Biol 5(9):a017947

    PubMed  PubMed Central  Google Scholar 

  • 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):11024–11029

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):794–805

    CAS  PubMed  PubMed Central  Google Scholar 

  • Soria G, Polo SE, Almouzni G (2012) Prime, repair, restore: the active role of chromatin in the DNA damage response. Mol Cell 46(6):722–734

    CAS  PubMed  Google Scholar 

  • 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):577–587

    CAS  PubMed  Google Scholar 

  • 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):163–175

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):336–347

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):267–272

    CAS  PubMed  Google Scholar 

  • 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):3217–3227

    CAS  PubMed  Google Scholar 

  • 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):105–117

    CAS  PubMed  Google Scholar 

  • Thomas SN, Yang AJ (2017) Mass spectrometry analysis of lysine posttranslational modifications of tau protein from Alzheimer’s disease brain. Methods Mol Biol 1523:161–177

    CAS  PubMed  PubMed Central  Google Scholar 

  • van der Horst A, Burgering BM (2007) Stressing the role of FoxO proteins in lifespan and disease. Nat Rev Mol Cell Biol 8(6):440–450

    PubMed  Google Scholar 

  • 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):1208–1211

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):467–476

    CAS  PubMed  Google Scholar 

  • 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):978–988

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):5516–5521

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):214–225

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):3683

    PubMed  PubMed Central  Google Scholar 

  • 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

  • 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):3070–3084

    CAS  PubMed  Google Scholar 

  • 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):1425–1433

    CAS  PubMed  Google Scholar 

  • 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):467–481

    CAS  PubMed  Google Scholar 

  • 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):2969–2980

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):139–146

    CAS  PubMed  Google Scholar 

  • 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):371–377

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):867–877

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):221–231

    CAS  PubMed  Google Scholar 

  • 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):e49267

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):484–497

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):305–320

    CAS  PubMed  Google Scholar 

  • 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):1700300

    Google Scholar 

  • 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 7:10810

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zinovkina LA (2018) Mechanisms of mitochondrial DNA repair in mammals. Biochemistry (Mosc) 83(3):233–249

    CAS  Google Scholar 

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Acknowledgments

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

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

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  1. Department of Biochemistry, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, PIN-695011, India

    Madhusoodanan Urulangodi

  2. Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, PIN-110085, India

    Abhishek Mohanty

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

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Urulangodi, M., Mohanty, A. DNA damage response and repair pathway modulation by non-histone protein methylation: implications in neurodegeneration. J. Cell Commun. Signal. 14, 31–45 (2020). https://doi.org/10.1007/s12079-019-00538-2

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