Protein-lysine methyltransferases G9a and GLP1 promote responses to DNA damage

Vasudeva Ginjala, Lizahira Rodriguez-Colon, Bratati Ganguly, Prawallika Gangidi, Paul Gallina, Husam Al-Hraishawi, Atul Kulkarni, Jeremy Tang, Jinesh Gheeya, Srilatha Simhadri, Ming Yao, Bing Xia, Shridar Ganesan

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Upon induction of DNA breaks, ATM activation leads to a cascade of local chromatin modifications that promote efficient recruitment of DNA repair proteins. Errors in this DNA repair pathway lead to genomic instability and cancer predisposition. Here, we show that the protein lysine methyltransferase G9a (also known as EHMT2) and GLP1 (also known as EHMT1) are critical components of the DNA repair pathway. G9a and GLP1 rapidly localizes to DNA breaks, with GLP1 localization being dependent on G9a. ATM phosphorylation of G9a on serine 569 is required for its recruitment to DNA breaks. G9a catalytic activity is required for the early recruitment of DNA repair factors including 53BP and BRCA1 to DNA breaks. Inhibition of G9a catalytic activity disrupts DNA repair pathways and increases sensitivity to ionizing radiation. Thus, G9a is a potential therapeutic target in the DNA repair pathway.

Original languageEnglish (US)
Article number16613
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

All Science Journal Classification (ASJC) codes

  • General

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