Protein-lysine methyltransferases G9a and GLP1 promote responses to DNA damage
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 methyltr...
Guardado en:
| Autores principales: | , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2017
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/4981bcc1f4d943a6816b9de984a70298 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:4981bcc1f4d943a6816b9de984a70298 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:4981bcc1f4d943a6816b9de984a702982021-12-02T15:05:03ZProtein-lysine methyltransferases G9a and GLP1 promote responses to DNA damage10.1038/s41598-017-16480-52045-2322https://doaj.org/article/4981bcc1f4d943a6816b9de984a702982017-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-16480-5https://doaj.org/toc/2045-2322Abstract 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.Vasudeva GinjalaLizahira Rodriguez-ColonBratati GangulyPrawallika GangidiPaul GallinaHusam Al-HraishawiAtul KulkarniJeremy TangJinesh GheeyaSrilatha SimhadriMing YaoBing XiaShridar GanesanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q 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 Protein-lysine methyltransferases G9a and GLP1 promote responses to DNA damage |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Vasudeva Ginjala |
| title |
Protein-lysine methyltransferases G9a and GLP1 promote responses to DNA damage |
| title_short |
Protein-lysine methyltransferases G9a and GLP1 promote responses to DNA damage |
| title_full |
Protein-lysine methyltransferases G9a and GLP1 promote responses to DNA damage |
| title_fullStr |
Protein-lysine methyltransferases G9a and GLP1 promote responses to DNA damage |
| title_full_unstemmed |
Protein-lysine methyltransferases G9a and GLP1 promote responses to DNA damage |
| title_sort |
protein-lysine methyltransferases g9a and glp1 promote responses to dna damage |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/4981bcc1f4d943a6816b9de984a70298 |
| work_keys_str_mv |
AT vasudevaginjala proteinlysinemethyltransferasesg9aandglp1promoteresponsestodnadamage AT lizahirarodriguezcolon proteinlysinemethyltransferasesg9aandglp1promoteresponsestodnadamage AT bratatiganguly proteinlysinemethyltransferasesg9aandglp1promoteresponsestodnadamage AT prawallikagangidi proteinlysinemethyltransferasesg9aandglp1promoteresponsestodnadamage AT paulgallina proteinlysinemethyltransferasesg9aandglp1promoteresponsestodnadamage AT husamalhraishawi proteinlysinemethyltransferasesg9aandglp1promoteresponsestodnadamage AT atulkulkarni proteinlysinemethyltransferasesg9aandglp1promoteresponsestodnadamage AT jeremytang proteinlysinemethyltransferasesg9aandglp1promoteresponsestodnadamage AT jineshgheeya proteinlysinemethyltransferasesg9aandglp1promoteresponsestodnadamage AT srilathasimhadri proteinlysinemethyltransferasesg9aandglp1promoteresponsestodnadamage AT mingyao proteinlysinemethyltransferasesg9aandglp1promoteresponsestodnadamage AT bingxia proteinlysinemethyltransferasesg9aandglp1promoteresponsestodnadamage AT shridarganesan proteinlysinemethyltransferasesg9aandglp1promoteresponsestodnadamage |
| _version_ |
1718388951979393024 |