| First Author | Van Meter M | Year | 2016 |
| Journal | Cell Rep | Volume | 16 |
| Issue | 10 | Pages | 2641-2650 |
| PubMed ID | 27568560 | Mgi Jnum | J:239021 |
| Mgi Id | MGI:5824783 | Doi | 10.1016/j.celrep.2016.08.006 |
| Citation | jnlVan Meter M, 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 Rep 16(10):2641-50 |
| abstractText | 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. |
