Synergy between SIRT1 and SIRT6 helps recognize DNA breaks and potentiates the DNA damage response and repair in humans and mice
Open Access
- 15 June 2020
- journal article
- research article
- Published by eLife Sciences Publications, Ltd in eLife
Abstract
The DNA damage response (DDR) is a highly orchestrated process but how double-strand DNA breaks (DSBs) are initially recognized is unclear. Here, we show that polymerized SIRT6 deacetylase recognizes DSBs and potentiates the DDR in human and mouse cells. First, SIRT1 deacetylates SIRT6 at residue K33, which is important for SIRT6 polymerization and mobilization toward DSBs. Then, K33-deacetylated SIRT6 anchors to γH2AX, allowing its retention on and subsequent remodeling of local chromatin. We show that a K33R mutation that mimics hypoacetylated SIRT6 can rescue defective DNA repair as a result of SIRT1 deficiency in cultured cells. These data highlight the synergistic action between SIRTs in the spatiotemporal regulation of the DDR and DNA repair in humans and mice.Keywords
Funding Information
- National Key R&D Program of China (2017YFA0503900)
- National Natural Science Foundation of China (91849208)
- National Natural Science Foundation of China (91949124)
- National Natural Science Foundation of China (81972602)
- National Natural Science Foundation of China (81702909)
- National Natural Science Foundation of China (81871114)
- National Natural Science Foundation of China (81601215)
- Natural Science Foundation of Guangdong Province (2015A030308007)
- Natural Science Foundation of Guangdong Province (2017B030301016)
- Shenzhen Science and Technology Innovation Commission (ZDSYS20190902093401689)
- Shenzhen Science and Technology Innovation Commission (JCYJ20180507182044945)
- Shenzhen Science and Technology Innovation Commission (KQJSCX20180328093403969)
- Tianjin MunicipalScience Foundation for Youths (18JCQNJC79800)
- Tianjin Medical University (B1714)
- National Natural Science Foundation of China (31530016)
- National Natural Science Foundation of China (31761133012)
- Shenzhen Science and Technology Innovation Commission (JCYJ20180507182213033)
- Shenzhen Science and Technology Innovation Commission (JCYJ20170412113009742)
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