Van Meter, MichaelSimon, MatthewTombline, GregoryMay, AlfredMorello, Timothy D.Hubbard, Basil P.Bredbenner, KatiePark, RosaSinclair, DavidBohr, Vilhelm A.Gorbunova, VeraSeluanov, Andrei2017-12-052016Van Meter, M., M. Simon, G. Tombline, A. May, T. D. Morello, B. P. Hubbard, K. Bredbenner, et al. 2016. “JNK Phosphorylates SIRT6 to Stimulate DNA Double-Strand Break Repair in Response to Oxidative Stress by Recruiting PARP1 to DNA Breaks.” Cell reports 16 (10): 2641-2650. doi:10.1016/j.celrep.2016.08.006. http://dx.doi.org/10.1016/j.celrep.2016.08.006.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34491931SUMMARY 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.en-USJournal Article2017-12-0510.1016/j.celrep.2016.08.006