DOI QR코드

DOI QR Code

SET7-mediated TIP60 methylation is essential for DNA double-strand break repair

  • Song Hyun, Kim (Department of Life Science, College of Natural Sciences, Chung-Ang University) ;
  • Junyoung, Park (Department of Life Science, College of Natural Sciences, Chung-Ang University) ;
  • Jin Woo, Park (Department of Life Science, College of Natural Sciences, Chung-Ang University) ;
  • Ja Young, Hahm (Department of Life Science, College of Natural Sciences, Chung-Ang University) ;
  • Seobin, Yoon (Department of Life Science, College of Natural Sciences, Chung-Ang University) ;
  • In Jun, Hwang (Department of Life Science, College of Natural Sciences, Chung-Ang University) ;
  • Keun Pil, Kim (Department of Life Science, College of Natural Sciences, Chung-Ang University) ;
  • Sang-Beom, Seo (Department of Life Science, College of Natural Sciences, Chung-Ang University)
  • 투고 : 2022.05.03
  • 심사 : 2022.07.05
  • 발행 : 2022.11.30

초록

The repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) is crucial for maintaining genomic integrity and is involved in numerous fundamental biological processes. Post-translational modifications by proteins play an important role in regulating DNA repair. Here, we report that the methyltransferase SET7 regulates HR-mediated DSB repair by methylating TIP60, a histone acetyltransferase and tumor suppressor involved in gene expression and protein stability. We show that SET7 targets TIP60 for methylation at K137, which facilitates DSB repair by promoting HR and determines cell viability against DNA damage. Interestingly, TIP60 demethylation is catalyzed by LSD1, which affects HR efficiency. Taken together, our findings reveal the importance of TIP60 methylation status by SET7 and LSD1 in the DSB repair pathway.

키워드

과제정보

This research was supported by the National Research Foundation of Korea (NRF) grant from the Ministry of Science, ICT & Future Planning [NRF-2021R1A2C1013553] and was supported by the Chung-Ang University Research Scholarship Grants in 2020.

참고문헌

  1. Heyer WD, Ehmsen KT and Liu J (2010) Regulation of homologous recombination in eukaryotes. Annu Rev Genet 44, 113-139 https://doi.org/10.1146/annurev-genet-051710-150955
  2. Zhao M, Geng R, Guo X et al (2017) PCAF/GCN5-mediated acetylation of RPA1 promotes nucleotide excision repair. Cell Rep 20, 1997-2009 https://doi.org/10.1016/j.celrep.2017.08.015
  3. Clarke TL, Sanchez-Bailon MP, Chiang K et al (2017) PRMT5-dependent methylation of the TIP60 coactivator RUVBL1 is a key regulator of homologous recombination. Mol Cell 65, 900-916 e907
  4. Park J and Lee DH (2020) Functional roles of protein phosphatase 4 in multiple aspects of cellular physiology: a friend and a foe. BMB Rep 53, 181-190 https://doi.org/10.5483/bmbrep.2020.53.4.019
  5. Sun Y, Jiang X and Price BD (2010) Tip60: connecting chromatin to DNA damage signaling. Cell Cycle 9, 930-936 https://doi.org/10.4161/cc.9.5.10931
  6. Yamamoto T and Horikoshi M (1997) Novel substrate specificity of the histone acetyltransferase activity of HIV-1-Tat interactive protein Tip60. J Biol Chem 272, 30595-30598 https://doi.org/10.1074/jbc.272.49.30595
  7. Sykes SM, Mellert HS, Holbert MA et al (2006) Acetylation of the p53 DNA-binding domain regulates apoptosis induction. Mol Cell 24, 841-851 https://doi.org/10.1016/j.molcel.2006.11.026
  8. Shi J, Wang Y, Zeng L et al (2014) Disrupting the interaction of BRD4 with diacetylated twist suppresses tumorigenesis in basal-like breast cancer. Cancer Cell 25, 210-225 https://doi.org/10.1016/j.ccr.2014.01.028
  9. Charvet C, Wissler M, Brauns-Schubert P et al (2011) Phosphorylation of Tip60 by GSK-3 determines the induction of PUMA and apoptosis by p53. Mol Cell 42, 584-596 https://doi.org/10.1016/j.molcel.2011.03.033
  10. Lin SY, Li TY, Liu Q et al (2012) GSK3-TIP60-ULK1 signaling pathway links growth factor deprivation to autophagy. Science 336, 477-481 https://doi.org/10.1126/science.1217032
  11. Sun Y, Jiang X, Chen S, Fernandes N and Price BD (2005) A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM. Proc Natl Acad Sci U S A 102, 13182-13187 https://doi.org/10.1073/pnas.0504211102
  12. Kassner I, Andersson A, Fey M, Tomas M, Ferrando-May E and Hottiger MO (2013) SET7/9-dependent methylation of ARTD1 at K508 stimulates poly-ADP-ribose formation after oxidative stress. Open Biol 3, 120173
  13. Hahm JY, Kim JY, Park JW et al (2019) Methylation of UHRF1 by SET7 is essential for DNA double-strand break repair. Nucleic Acids Res 47, 184-196 https://doi.org/10.1093/nar/gky975
  14. Barsyte-Lovejoy D, Li F, Oudhoff MJ et al (2014) (R)-PFI-2 is a potent and selective inhibitor of SETD7 methyltransferase activity in cells. Proc Natl Acad Sci U S A 111, 12853-12858 https://doi.org/10.1073/pnas.1407358111
  15. Koc A, Wheeler LJ, Mathews CK and Merrill GF (2004) Hydroxyurea arrests DNA replication by a mechanism that preserves basal dNTP pools. J Biol Chem 279, 223-230 https://doi.org/10.1074/jbc.M303952200
  16. Singh A and Xu YJ (2016) The cell killing mechanisms of hydroxyurea. Genes (Basel) 7, 99
  17. Lundin C, Erixon K, Arnaudeau C et al (2002) Different roles for nonhomologous end joining and homologous recombination following replication arrest in mammalian cells. Mol Cell Biol 22, 5869-5878 https://doi.org/10.1128/MCB.22.16.5869-5878.2002
  18. Rothkamm K, Kruger I, Thompson LH and Lobrich M (2003) Pathways of DNA double-strand break repair during the mammalian cell cycle. Mol Cell Biol 23, 5706-5715 https://doi.org/10.1128/MCB.23.16.5706-5715.2003
  19. Nishioka K, Chuikov S, Sarma K et al (2002) Set9, a novel histone H3 methyltransferase that facilitates transcription by precluding histone tail modifications required for heterochromatin formation. Genes Dev 16, 479-489 https://doi.org/10.1101/gad.967202
  20. Culhane JC and Cole PA (2007) LSD1 and the chemistry of histone demethylation. Curr Opin Chem Biol 11, 561-568 https://doi.org/10.1016/j.cbpa.2007.07.014
  21. Wang J, Hevi S, Kurash JK et al (2009) The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation. Nat Genet 41, 125-129 https://doi.org/10.1038/ng.268
  22. Mattera L, Escaffit F, Pillaire MJ et al (2009) The p400/Tip60 ratio is critical for colorectal cancer cell proliferation through DNA damage response pathways. Oncogene 28, 1506-1517 https://doi.org/10.1038/onc.2008.499
  23. Halkidou K, Gnanapragasam VJ, Mehta PB et al (2003) Expression of Tip60, an androgen receptor coactivator, and its role in prostate cancer development. Oncogene 22, 2466-2477 https://doi.org/10.1038/sj.onc.1206342
  24. Gorrini C, Squatrito M, Luise C et al (2007) Tip60 is a haplo-insufficient tumour suppressor required for an oncogene-induced DNA damage response. Nature 448, 1063-1067 https://doi.org/10.1038/nature06055
  25. Hishikawa A, Hayashi K, Abe T et al (2019) Decreased KAT5 expression impairs DNA repair and induces altered DNA methylation in kidney podocytes. Cell Rep 26, 1318-1332 e1314
  26. Kontaki H and Talianidis I (2010) Lysine methylation regulates E2F1-induced cell death. Mol Cell 39, 152-160 https://doi.org/10.1016/j.molcel.2010.06.006
  27. Liu X, Wang D, Zhao Y et al (2011) Methyltransferase Set7/9 regulates p53 activity by interacting with Sirtuin 1 (SIRT1). Proc Natl Acad Sci U S A 108, 1925-1930 https://doi.org/10.1073/pnas.1019619108
  28. Hahm JY, Kang JY, Park JW, Jung H and Seo SB (2020) Methylated-UHRF1 and PARP1 interaction is critical for homologous recombination. BMB Rep 53, 112-117 https://doi.org/10.5483/bmbrep.2020.53.2.264
  29. Mosammaparast N, Kim H, Laurent B et al (2013) The histone demethylase LSD1/KDM1A promotes the DNA damage response. Journal of Cell Biology 203, 457-470 https://doi.org/10.1083/jcb.201302092