Identification of a Novel DNA Oxidative Damage Repair Pathway, Requiring the Ubiquitination of the Histone Variant MacroH2A1.1

Overview

Journal BMC Biol

Publisher Biomed Central

Specialty Biology

Date 2024 Sep 1

PMID 39218869

Authors

Khalid Ouararhni

Flore Mietton

Jamal S M Sabir

Abdulkhaleg Ibrahim

Annie Molla

Raed S Albheyri

Ali T Zari

Ahmed Bahieldin

Herve Menoni

Christian Bronner

Stefan Dimitrov

Ali Hamiche

Affiliations

Soon will be listed here.

Abstract

Background: The histone variant macroH2A (mH2A), the most deviant variant, is about threefold larger than the conventional histone H2A and consists of a histone H2A-like domain fused to a large Non-Histone Region responsible for recruiting PARP-1 to chromatin. The available data suggest that the histone variant mH2A participates in the regulation of transcription, maintenance of heterochromatin, NAD metabolism, and double-strand DNA repair.

Results: Here, we describe a novel function of mH2A, namely its implication in DNA oxidative damage repair through PARP-1. The depletion of mH2A affected both repair and cell survival after the induction of oxidative lesions in DNA. PARP-1 formed a specific complex with mH2A nucleosomes in vivo. The mH2A nucleosome-associated PARP-1 is inactive. Upon oxidative damage, mH2A is ubiquitinated, PARP-1 is released from the mH2A nucleosomal complex, and is activated. The in vivo-induced ubiquitination of mH2A, in the absence of any oxidative damage, was sufficient for the release of PARP-1. However, no release of PARP-1 was observed upon treatment of the cells with either the DNA alkylating agent MMS or doxorubicin.

Conclusions: Our data identify a novel pathway for the repair of DNA oxidative lesions, requiring the ubiquitination of mH2A for the release of PARP-1 from chromatin and its activation.

References

DAmours D, Desnoyers S, DSilva I, Poirier G . Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem J. 1999; 342 ( Pt 2):249-68. PMC: 1220459. View

Schreiber V, Dantzer F, Ame J, de Murcia G . Poly(ADP-ribose): novel functions for an old molecule. Nat Rev Mol Cell Biol. 2006; 7(7):517-28. DOI: 10.1038/nrm1963. View

Ouararhni K, Hadj-Slimane R, Ait-Si-Ali S, Robin P, Mietton F, Harel-Bellan A . The histone variant mH2A1.1 interferes with transcription by down-regulating PARP-1 enzymatic activity. Genes Dev. 2006; 20(23):3324-36. PMC: 1686608. DOI: 10.1101/gad.396106. View

Posavec Marjanovic M, Hurtado-Bages S, Lassi M, Valero V, Malinverni R, Delage H . MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD consumption. Nat Struct Mol Biol. 2017; 24(11):902-910. PMC: 5791885. DOI: 10.1038/nsmb.3481. View

Pliatska M, Kapasa M, Kokkalis A, Polyzos A, Thanos D . The Histone Variant MacroH2A Blocks Cellular Reprogramming by Inhibiting Mesenchymal-to-Epithelial Transition. Mol Cell Biol. 2018; 38(10). PMC: 5954199. DOI: 10.1128/MCB.00669-17. View

Nusinow D, Hernandez-Munoz I, Fazzio T, Shah G, Kraus W, Panning B . Poly(ADP-ribose) polymerase 1 is inhibited by a histone H2A variant, MacroH2A, and contributes to silencing of the inactive X chromosome. J Biol Chem. 2007; 282(17):12851-9. DOI: 10.1074/jbc.M610502200. View

Menoni H, Shukla M, Gerson V, Dimitrov S, Angelov D . Base excision repair of 8-oxoG in dinucleosomes. Nucleic Acids Res. 2011; 40(2):692-700. PMC: 3258150. DOI: 10.1093/nar/gkr761. View

Hodge D, Cui J, Gamble M, Guo W . Histone Variant MacroH2A1 Plays an Isoform-Specific Role in Suppressing Epithelial-Mesenchymal Transition. Sci Rep. 2018; 8(1):841. PMC: 5770377. DOI: 10.1038/s41598-018-19364-4. View

Bao Y, Konesky K, Park Y, Rosu S, Dyer P, Rangasamy D . Nucleosomes containing the histone variant H2A.Bbd organize only 118 base pairs of DNA. EMBO J. 2004; 23(16):3314-24. PMC: 514500. DOI: 10.1038/sj.emboj.7600316. View

10.

Obri A, Ouararhni K, Papin C, Diebold M, Padmanabhan K, Marek M . ANP32E is a histone chaperone that removes H2A.Z from chromatin. Nature. 2014; 505(7485):648-53. DOI: 10.1038/nature12922. View

11.

Shukla M, Hussain Syed S, Goutte-Gattat D, Charles Richard J, Montel F, Hamiche A . The docking domain of histone H2A is required for H1 binding and RSC-mediated nucleosome remodeling. Nucleic Acids Res. 2010; 39(7):2559-70. PMC: 3074127. DOI: 10.1093/nar/gkq1174. View

12.

Sarma K, Reinberg D . Histone variants meet their match. Nat Rev Mol Cell Biol. 2005; 6(2):139-49. DOI: 10.1038/nrm1567. View

13.

Angelov D, Verdel A, An W, Bondarenko V, Hans F, Doyen C . SWI/SNF remodeling and p300-dependent transcription of histone variant H2ABbd nucleosomal arrays. EMBO J. 2004; 23(19):3815-24. PMC: 522799. DOI: 10.1038/sj.emboj.7600400. View

14.

Khurana S, Kruhlak M, Kim J, Tran A, Liu J, Nyswaner K . A macrohistone variant links dynamic chromatin compaction to BRCA1-dependent genome maintenance. Cell Rep. 2014; 8(4):1049-62. PMC: 4154351. DOI: 10.1016/j.celrep.2014.07.024. View

15.

Drane P, Ouararhni K, Depaux A, Shuaib M, Hamiche A . The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3. Genes Dev. 2010; 24(12):1253-65. PMC: 2885661. DOI: 10.1101/gad.566910. View

16.

Poirier G, de Murcia G, Niedergang C, Mandel P . Poly(ADP-ribosyl)ation of polynucleosomes causes relaxation of chromatin structure. Proc Natl Acad Sci U S A. 1982; 79(11):3423-7. PMC: 346432. DOI: 10.1073/pnas.79.11.3423. View

17.

Shuaib M, Ouararhni K, Dimitrov S, Hamiche A . HJURP binds CENP-A via a highly conserved N-terminal domain and mediates its deposition at centromeres. Proc Natl Acad Sci U S A. 2010; 107(4):1349-54. PMC: 2824361. DOI: 10.1073/pnas.0913709107. View

18.

Latrick C, Marek M, Ouararhni K, Papin C, Stoll I, Ignatyeva M . Molecular basis and specificity of H2A.Z-H2B recognition and deposition by the histone chaperone YL1. Nat Struct Mol Biol. 2016; 23(4):309-16. DOI: 10.1038/nsmb.3189. View

19.

Costanzi C, Pehrson J . Histone macroH2A1 is concentrated in the inactive X chromosome of female mammals. Nature. 1998; 393(6685):599-601. DOI: 10.1038/31275. View

20.

Mietton F, Sengupta A, Molla A, Picchi G, Barral S, Heliot L . Weak but uniform enrichment of the histone variant macroH2A1 along the inactive X chromosome. Mol Cell Biol. 2008; 29(1):150-6. PMC: 2612491. DOI: 10.1128/MCB.00997-08. View