JMJD6 participates in the maintenance of ribosomal DNA integrity in response to DNA damage
Autoři:
Jérémie Fages aff001; Catherine Chailleux aff001; Jonathan Humbert aff002; Suk-Min Jang aff002; Jérémy Loehr aff003; Jean-Philippe Lambert aff003; Jacques Côté aff002; Didier Trouche aff001; Yvan Canitrot aff001
Působiště autorů:
LBCMCP, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, Toulouse, France
aff001; Centre de Recherche sur le Cancer de l'Université Laval, axe Oncologie du Centre de recherche du CHU de Québec-Université Laval, Québec, Canada
aff002; Centre de Recherche sur le Cancer de l'Université Laval, axe Endocrinologie et néphrologie du Centre de recherche du CHU de Québec-Université Laval, Québec, Canada
aff003
Vyšlo v časopise:
JMJD6 participates in the maintenance of ribosomal DNA integrity in response to DNA damage. PLoS Genet 16(6): e32767. doi:10.1371/journal.pgen.1008511
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1008511
Souhrn
Ribosomal DNA (rDNA) is the most transcribed genomic region and contains hundreds of tandem repeats. Maintaining these rDNA repeats as well as the level of rDNA transcription is essential for cellular homeostasis. DNA damages generated in rDNA need to be efficiently and accurately repaired and rDNA repeats instability has been reported in cancer, aging and neurological diseases. Here, we describe that the histone demethylase JMJD6 is rapidly recruited to nucleolar DNA damage and is crucial for the relocalisation of rDNA in nucleolar caps. Yet, JMJD6 is dispensable for rDNA transcription inhibition. Mass spectrometry analysis revealed that JMJD6 interacts with the nucleolar protein Treacle and modulates its interaction with NBS1. Moreover, cells deficient for JMJD6 show increased sensitivity to nucleolar DNA damage as well as loss and rearrangements of rDNA repeats upon irradiation. Altogether our data reveal that rDNA transcription inhibition is uncoupled from rDNA relocalisation into nucleolar caps and that JMJD6 is required for rDNA stability through its role in nucleolar caps formation.
Klíčová slova:
Cell staining – DNA damage – DNA transcription – Histones – Ionizing radiation – Non-homologous end joining – Small interfering RNAs – Nucleolus
Zdroje
1. Iyama T, Wilson DM 3rd (2013) DNA repair mechanisms in dividing and non-dividing cells. DNA Repair (Amst) 12: 620–636.
2. McStay B (2016) Nucleolar organizer regions: genomic 'dark matter' requiring illumination. Genes Dev 30: 1598–1610. doi: 10.1101/gad.283838.116 27474438
3. Grummt I (2013) The nucleolus-guardian of cellular homeostasis and genome integrity. Chromosoma 122: 487–497. doi: 10.1007/s00412-013-0430-0 24022641
4. Udugama M, Sanij E, Voon HPJ, Son J, Hii L, et al. (2018) Ribosomal DNA copy loss and repeat instability in ATRX-mutated cancers. Proc Natl Acad Sci U S A 115: 4737–4742. doi: 10.1073/pnas.1720391115 29669917
5. Killen MW, Stults DM, Adachi N, Hanakahi L, Pierce AJ (2009) Loss of Bloom syndrome protein destabilizes human gene cluster architecture. Hum Mol Genet 18: 3417–3428. doi: 10.1093/hmg/ddp282 19542097
6. Stults DM, Killen MW, Williamson EP, Hourigan JS, Vargas HD, et al. (2009) Human rRNA gene clusters are recombinational hotspots in cancer. Cancer Res 69: 9096–9104. doi: 10.1158/0008-5472.CAN-09-2680 19920195
7. Larsen DH, Stucki M (2015) Nucleolar responses to DNA double-strand breaks. Nucleic Acids Res 44: 538–544. doi: 10.1093/nar/gkv1312 26615196
8. Warmerdam DO, Wolthuis RMF (2019) Keeping ribosomal DNA intact: a repeating challenge. Chromosome Res 27: 57–72. doi: 10.1007/s10577-018-9594-z 30556094
9. Harding SM, Boiarsky JA, Greenberg RA (2015) ATM Dependent Silencing Links Nucleolar Chromatin Reorganization to DNA Damage Recognition. Cell Rep 13: 251–259. doi: 10.1016/j.celrep.2015.08.085 26440899
10. Warmerdam DO, van den Berg J, Medema RH (2016) Breaks in the 45S rDNA Lead to Recombination-Mediated Loss of Repeats. Cell Rep 14: 2519–2527. doi: 10.1016/j.celrep.2016.02.048 26972008
11. Kruhlak M, Crouch EE, Orlov M, Montano C, Gorski SA, et al. (2007) The ATM repair pathway inhibits RNA polymerase I transcription in response to chromosome breaks. Nature 447: 730–734. doi: 10.1038/nature05842 17554310
12. Korsholm LM, Gal Z, Lin L, Quevedo O, Ahmad DA, et al. (2019) Double-strand breaks in ribosomal RNA genes activate a distinct signaling and chromatin response to facilitate nucleolar restructuring and repair. Nucleic Acids Res 47: 8019–8035. doi: 10.1093/nar/gkz518 31184714
13. van Sluis M, McStay B (2015) A localized nucleolar DNA damage response facilitates recruitment of the homology-directed repair machinery independent of cell cycle stage. Genes Dev 29: 1151–1163. doi: 10.1101/gad.260703.115 26019174
14. Mooser C, Symeonidou IE, Leimbacher PA, Ribeiro A, Shorrocks AK, et al. (2020) Treacle controls the nucleolar response to rDNA breaks via TOPBP1 recruitment and ATR activation. Nat Commun 11: 123. doi: 10.1038/s41467-019-13981-x 31913317
15. Velichko AK, Petrova NV, Luzhin AV, Strelkova OS, Ovsyannikova N, et al. (2019) Hypoosmotic stress induces R loop formation in nucleoli and ATR/ATM-dependent silencing of nucleolar transcription. Nucleic Acids Res 47: 6811–6825. doi: 10.1093/nar/gkz436 31114877
16. Aymard F, Bugler B, Schmidt CK, Guillou E, Caron P, et al. (2016) Transcriptionally active chromatin recruits homologous recombination at DNA double-strand breaks. Nat Struct Mol Biol 21: 366–374.
17. Luijsterburg MS, de Krijger I, Wiegant WW, Shah RG, Smeenk G, et al. (2016) PARP1 Links CHD2-Mediated Chromatin Expansion and H3.3 Deposition to DNA Repair by Non-homologous End-Joining. Mol Cell 61: 547–562. doi: 10.1016/j.molcel.2016.01.019 26895424
18. Clouaire T, Legube G (2015) DNA double strand break repair pathway choice: a chromatin based decision? Nucleus 6: 107–113. doi: 10.1080/19491034.2015.1010946 25675367
19. Chang B, Chen Y, Zhao Y, Bruick RK (2007) JMJD6 is a histone arginine demethylase. Science 318: 444–447. doi: 10.1126/science.1145801 17947579
20. Wang F, He L, Huangyang P, Liang J, Si W, et al. (2014) JMJD6 promotes colon carcinogenesis through negative regulation of p53 by hydroxylation. PLoS Biol 12: e1001819. doi: 10.1371/journal.pbio.1001819 24667498
21. Webby CJ, Wolf A, Gromak N, Dreger M, Kramer H, et al. (2009) Jmjd6 catalyses lysyl-hydroxylation of U2AF65, a protein associated with RNA splicing. Science 325: 90–93. doi: 10.1126/science.1175865 19574390
22. Liu Y, Long YH, Wang SQ, Zhang YY, Li YF, et al. (2018) JMJD6 regulates histone H2A.X phosphorylation and promotes autophagy in triple-negative breast cancer cells via a novel tyrosine kinase activity. Oncogene 38: 980–927. doi: 10.1038/s41388-018-0466-y 30185813
23. Huo D, Chen H, Cheng Y, Song X, Zhang K, et al. (2019) JMJD6 modulates DNA damage response through downregulating H4K16ac independently of its enzymatic activity. Cell Death Differ 27: 1052–1066. doi: 10.1038/s41418-019-0397-3 31358914
24. Agudelo D, Duringer A, Bozoyan L, Huard CC, Carter S, et al. (2017) Marker-free coselection for CRISPR-driven genome editing in human cells. Nat Methods 14: 615–620. doi: 10.1038/nmeth.4265 28417998
25. Kwok J, O'Shea M, Hume DA, Lengeling A(2017) Jmjd6, a JmjC Dioxygenase with Many Interaction Partners and Pleiotropic Functions. Front Genet 8: 32. doi: 10.3389/fgene.2017.00032 28360925
26. Wolf A, Mantri M, Heim A, Muller U, Fichter E, et al. (2013) The polyserine domain of the lysyl-5 hydroxylase Jmjd6 mediates subnuclear localization. Biochem J 453: 357–370. doi: 10.1042/BJ20130529 23688307
27. Ciccia A, Huang JW, Izhar L, Sowa ME, Harper JW, et al. (2014) Treacher Collins syndrome TCOF1 protein cooperates with NBS1 in the DNA damage response. Proc Natl Acad Sci U S A 111: 18631–18636. doi: 10.1073/pnas.1422488112 25512513
28. Larsen DH, Hari F, Clapperton JA, Gwerder M, Gutsche K, et al. (2014) The NBS1-Treacle complex controls ribosomal RNA transcription in response to DNA damage. Nat Cell Biol 16: 792–803. doi: 10.1038/ncb3007 25064736
29. Iacovoni JS, Caron P, Lassadi I, Nicolas E, Massip L, et al. (2010) High-resolution profiling of gammaH2AX around DNA double strand breaks in the mammalian genome. EMBO J 29: 1446–1457. doi: 10.1038/emboj.2010.38 20360682
30. Marnef A, Finoux A, Arnould C, Guillou E, Daburon V, et al. (2019) A cohesin/HUSH and LINC-dependent pathway controls ribosomal DNA double strand break repair. Genes Dev 33: 1175–1190. doi: 10.1101/gad.324012.119 31395742
31. Rahman S, Sowa ME, Ottinger M, Smith JA, Shi Y, et al. (2011) The Brd4 extraterminal domain confers transcription activation independent of pTEFb by recruiting multiple proteins, including NSD3. Mol Cell Biol 31: 2641–2652. doi: 10.1128/MCB.01341-10 21555454
32. Komatsu K (2016) NBS1 and multiple regulations of DNA damage response. J Radiat Res 57 Suppl 1: i11–i17.
33. Floutsakou I, Agrawal S, Nguyen TT, Seoighe C, Ganley AR, et al. (2013) The shared genomic architecture of human nucleolar organizer regions. Genome Res 23: 2003–2012. doi: 10.1101/gr.157941.113 23990606
34. Chang CF, Chu PC, Wu PY, Yu MY, Lee JY, et al. (2015) PHRF1 promotes genome integrity by modulating non-homologous end-joining. Cell Death Dis 6: e1716. doi: 10.1038/cddis.2015.81 25855964
35. Dalvai M, Loehr J, Jacquet K, Huard CC, Roques C, et al. (2015) A Scalable Genome-Editing-Based Approach for Mapping Multiprotein Complexes in Human Cells. Cell Rep 13: 621–633. doi: 10.1016/j.celrep.2015.09.009 26456817
36. Lambert JP, Tucholska M, Go C, Knight JD, Gingras AC (2015) Proximity biotinylation and affinity purification are complementary approaches for the interactome mapping of chromatin-associated protein complexes. J Proteomics 118: 81–94. doi: 10.1016/j.jprot.2014.09.011 25281560
37. Taty-Taty GC, Courilleau C, Quaranta M, Carayon A, Chailleux C, et al. (2014) H2A.Z depletion impairs proliferation and viability but not DNA double-strand breaks repair in human immortalized and tumoral cell lines. Cell Cycle 13: 399–407. doi: 10.4161/cc.27143 24240188
38. Doyon Y, Cote J (2016) Preparation and Analysis of Native Chromatin-Modifying Complexes. Methods Enzymol 573: 303–318. doi: 10.1016/bs.mie.2016.01.017 27372759
39. Abmayr SM, Yao T, Parmely T, Workman JL (2006) Preparation of nuclear and cytoplasmic extracts from mammalian cells. Curr Protoc Mol Biol Chapter 12: Unit 12 11.
40. Rappsilber J, Mann M, Ishihama Y (2007) Protocol for micro-purification, enrichment, pre-fractionation and storage of peptides for proteomics using StageTips. Nat Protoc 2: 1896–1906. doi: 10.1038/nprot.2007.261 17703201
41. Liu G, Knight JD, Zhang JP, Tsou CC, Wang J, et al. (2016) Data Independent Acquisition analysis in ProHits 4.0. J Proteomics 149: 64–68. doi: 10.1016/j.jprot.2016.04.042 27132685
42. Kessner D, Chambers M, Burke R, Agus D, Mallick P (2008) ProteoWizard: open source software for rapid proteomics tools development. Bioinformatics 24: 2534–2536. doi: 10.1093/bioinformatics/btn323 18606607
43. Deutsch EW, Mendoza L, Shteynberg D, Slagel J, Sun Z, et al. (2015) Trans-Proteomic Pipeline, a standardized data processing pipeline for large-scale reproducible proteomics informatics. Proteomics Clin Appl 9: 745–754. doi: 10.1002/prca.201400164 25631240
44. Shteynberg D, Deutsch EW, Lam H, Eng JK, Sun Z, et al. (2011) iProphet: multi-level integrative analysis of shotgun proteomic data improves peptide and protein identification rates and error estimates. Mol Cell Proteomics 10: M111 007690.
45. Courilleau C, Chailleux C, Jauneau A, Grimal F, Briois S, et al. (2012) The chromatin remodeler p400 ATPase facilitates Rad51-mediated repair of DNA double-strand breaks. J Cell Biol 199: 1067–1081. doi: 10.1083/jcb.201205059 23266955
46. Puget N, Knowlton M, Scully R (2005) Molecular analysis of sister chromatid recombination in mammalian cells. DNA Repair (Amst) 4: 149–161.
47. Taty-Taty GC, Chailleux C, Quaranta M, So A, Guirouilh-Barbat J, et al. (2016) Control of alternative end joining by the chromatin remodeler p400 ATPase. Nucleic Acids Res 44: 1657–1668. doi: 10.1093/nar/gkv1202 26578561
48. Xie A, Kwok A, Scully R (2009) Role of mammalian Mre11 in classical and alternative nonhomologous end joining. Nat Struct Mol Biol 16: 814–818. doi: 10.1038/nsmb.1640 19633669
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