细胞生物学
抄写(语言学)
DNA
DNA损伤
DNA修复
生物
化学
遗传学
语言学
哲学
作者
Sarallah Rezazadeh,David Yang,Seyed Ali Biashad,Denis Firsanov,Masaki Takasugi,Michael Gilbert,Gregory Tombline,Natarajan V. Bhanu,Benjamin A. Garcia,Andrei Seluanov,Vera Gorbunova
出处
期刊:Aging
[Impact Journals, LLC]
日期:2020-06-25
卷期号:12 (12): 11165-11184
被引量:26
标识
DOI:10.18632/aging.103567
摘要
When transcribed DNA is damaged, the transcription and DNA repair machineries must interact to ensure successful DNA repair. The mechanisms of this interaction in the context of chromatin are still being elucidated. Here we show that the SIRT6 protein enhances non-homologous end joining (NHEJ) DNA repair by transiently repressing transcription. Specifically, SIRT6 mono-ADP ribosylates the lysine demethylase JHDM1A/KDM2A leading to rapid displacement of KDM2A from chromatin, resulting in increased H3K36me2 levels. Furthermore, we found that through HP1α binding, H3K36me2 promotes subsequent H3K9 tri-methylation. This results in transient suppression of transcription initiation by RNA polymerase II and recruitment of NHEJ factors to DNA double-stranded breaks (DSBs). These data reveal a mechanism where SIRT6 mediates a crosstalk between transcription and DNA repair machineries to promote DNA repair. SIRT6 functions in multiple pathways related to aging, and its novel function coordinating DNA repair and transcription is yet another way by which SIRT6 promotes genome stability and longevity.
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