2. Academic Validation
  3. SIRT7 promotes genome integrity and modulates non-homologous end joining DNA repair

SIRT7 promotes genome integrity and modulates non-homologous end joining DNA repair

  • EMBO J. 2016 Jul 15;35(14):1488-503. doi: 10.15252/embj.201593499.
Berta N Vazquez 1,  Joshua K Thackray 1,  Nicolas G Simonet 2,  Noriko Kane-Goldsmith 1,  Paloma Martinez-Redondo 2,  Trang Nguyen 1,  Samuel Bunting 3,  Alejandro Vaquero 2,  Jay A Tischfield 1,  Lourdes Serrano 4
Affiliations

Affiliations

  • 1 Department of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ, USA.
  • 2 Chromatin Biology Laboratory, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
  • 3 Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ, USA.
  • 4 Department of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ, USA [email protected].
PMID: 27225932 DOI: 10.15252/embj.201593499
Abstract

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.

Keywords

DNA damage; PARP1; SIRT7; histone acetylation; non‐homologous end joining.

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