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JNK Phosphorylates SIRT6 to Stimulate DNA Double-Strand Break Repair in Response to Oxidative Stress by Recruiting PARP1 to DNA Breaks.
- Source :
-
Cell reports [Cell Rep] 2016 Sep 06; Vol. 16 (10), pp. 2641-2650. Date of Electronic Publication: 2016 Aug 25. - Publication Year :
- 2016
-
Abstract
- The accumulation of damage caused by oxidative stress has been linked to aging and to the etiology of numerous age-related diseases. The longevity gene, sirtuin 6 (SIRT6), promotes genome stability by facilitating DNA repair, especially under oxidative stress conditions. Here we uncover the mechanism by which SIRT6 is activated by oxidative stress to promote DNA double-strand break (DSB) repair. We show that the stress-activated protein kinase, c-Jun N-terminal kinase (JNK), phosphorylates SIRT6 on serine 10 in response to oxidative stress. This post-translational modification facilitates the mobilization of SIRT6 to DNA damage sites and is required for efficient recruitment of poly (ADP-ribose) polymerase 1 (PARP1) to DNA break sites and for efficient repair of DSBs. Our results demonstrate a post-translational mechanism regulating SIRT6, and they provide the link between oxidative stress signaling and DNA repair pathways that may be critical for hormetic response and longevity assurance.<br /> (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adenosine Diphosphate Ribose metabolism
Animals
HEK293 Cells
Humans
Mice, Knockout
Models, Biological
Phosphorylation
Phosphoserine metabolism
DNA Breaks, Double-Stranded
DNA Repair
JNK Mitogen-Activated Protein Kinases metabolism
Oxidative Stress
Poly (ADP-Ribose) Polymerase-1 metabolism
Sirtuins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 16
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 27568560
- Full Text :
- https://doi.org/10.1016/j.celrep.2016.08.006