| First Author | Vazquez BN | Year | 2016 |
| Journal | EMBO J | Volume | 35 |
| Issue | 14 | Pages | 1488-503 |
| PubMed ID | 27225932 | Mgi Jnum | J:234105 |
| Mgi Id | MGI:5789069 | Doi | 10.15252/embj.201593499 |
| Citation | Vazquez BN, et al. (2016) SIRT7 promotes genome integrity and modulates non-homologous end joining DNA repair. EMBO J 35(14):1488-503 |
| abstractText | Sirtuins, a family of protein deacetylases, promote cellular homeostasis by mediating communication between cells and environment. The enzymatic activity of the mammalian sirtuin SIRT7 targets acetylated lysine in the N-terminal tail of histone H3 (H3K18Ac), thus modulating chromatin structure and transcriptional competency. SIRT7 deletion is associated with reduced lifespan in mice through unknown mechanisms. Here, we show that SirT7-knockout mice suffer from partial embryonic lethality and a progeroid-like phenotype. Consistently, SIRT7-deficient cells display increased replication stress and impaired DNA repair. SIRT7 is recruited in a PARP1-dependent manner to sites of DNA damage, where it modulates H3K18Ac levels. H3K18Ac in turn affects recruitment of the damage response factor 53BP1 to DNA double-strand breaks (DSBs), thereby influencing the efficiency of non-homologous end joining (NHEJ). These results reveal a direct role for SIRT7 in DSB repair and establish a functional link between SIRT7-mediated H3K18 deacetylation and the maintenance of genome integrity. |
