Abstract
DNA damage response (DDR) is a highly orchestrated process; initially how the DNA breaks are recognized need in-depth study. Here, we show that polymerized SIRT6 deacetylase recognizes double-strand DNA breaks (DSBs) and potentiates DDR. SIRT1 deacetylates SIRT6 at residue K33, which is important for SIRT6 polymerization and mobilization toward DNA breaks. The K33-deacetylated SIRT6 anchors to γH2AX, allowing its retention on and subsequent remodeling of local chromatin. The K33R mutation, mimicking hypoacetylated SIRT6, rescues defective DNA repair imposed by SIRT1 deficiency in cells. Our data highlights a synergistic action of SIRTs in spatiotemporal regulation of DDR and DNA repair.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.








