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Cell Rep. 2016 Sep 6;16(10):2641-2650. doi: 10.1016/j.celrep.2016.08.006. Epub 2016 Aug 25.

JNK Phosphorylates SIRT6 to Stimulate DNA Double-Strand Break Repair in Response to Oxidative Stress by Recruiting PARP1 to DNA Breaks.

Author information

1
Department of Biology, University of Rochester, Rochester, NY 14627, USA.
2
Laboratory of Molecular Gerontology, National Institute on Aging, Baltimore, MD 21224, USA.
3
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
4
Department of Biology, University of Rochester, Rochester, NY 14627, USA. Electronic address: vera.gorbunova@rochester.edu.
5
Department of Biology, University of Rochester, Rochester, NY 14627, USA. Electronic address: andrei.seluanov@rochester.edu.

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.

PMID:
27568560
PMCID:
PMC5089070
DOI:
10.1016/j.celrep.2016.08.006
[Indexed for MEDLINE]
Free PMC Article

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