SIRT6 promotes DNA repair under stress by activating PARP1

By Z. Mao, Christopher M. Hine, Xiao Tian, M. Van Meter, M. Au, Amita Vaidya, Andrei Seluanov, Vera Gorbunova. Science, 2011

854 citations recorded by the source corpus.

A genome stability regulator integrates DNA repair and stress signaling pathways. Sirtuin 6 (SIRT6) is a mammalian homolog of the yeast Sir2 deacetylase. Mice deficient for SIRT6 exhibit genome instability. Here, we show that in mammalian cells subjected to oxidative stress SIRT6 is recruited to the sites of DNA double-strand breaks (DSBs) and stimulates DSB repair, through both nonhomologous end joining and homologous recombination. Our results indicate that SIRT6 physically associates with poly[adenosine diphosphate (ADP)–ribose] polymerase 1 (PARP1) and mono-ADP-ribosylates PARP1 on lysine residue 521, thereby stimulating PARP1 poly-ADP-ribosylase activity and enhancing DSB repair under oxidative stress.

Subfields: Geriatrics and Gerontology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/c06e014ad23669d7afce861915780b10ec9ecd4c

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Geriatrics and Gerontology

In Molecular Biology

In Oncology

Citations in the corpus

THE HISTONE DEACETYLASE SIRT6 IS A NOVEL TUMOR SUPPRESSOR THAT CONTROLS CANCER METABOLISM (2012, positive): “…DNA double-strand break (DSB) repair by regulating the activity of C-terminal binding protein (CtBP) interacting protein (CtIP) (Kaidi et al., 2010) and poly[adenosine diphosphate (ADP)-ribose] polymerase 1 (PARP1) (Mao et al., 2011), further supporting a role for SIRT6 as a key DNA repair factor.”
On PAR with PARP: cellular stress signaling through poly(ADP-ribose) and PARP-1. (2012, background): “Point mutations that eliminate both the deacetylation and mono(ADP-ribosyl)ation activities of SIRT6 abolish the function of SIRT6 in DNA damage repair (Mao et al. 2011).”
NAD+ metabolism and the control of energy homeostasis - a balancing act between mitochondria and the nucleus (2015, background): “Furthermore, SIRT6, which, as described above, most likely does not act as anNAD+ sensor (see NAD+-Consuming Enzymes (I): Sirtuins), can activate PARP1 to stimulate highly efficient double-strand break repair, but only in response to oxidative-stressinduced DNA damage (Mao et al., 2011).”
Therapeutic potential of NAD-boosting molecules: the in vivo evidence (2018, positive): “SIRT6 modifies PARP1 by mono-ADP-ribosylation, thereby increasing double-strand DNA break repair (Mao et al., 2011), whereas inhibition of PARP1 increases expression of SIRT1, SIRT4, and SIRT6 (Wencel et al., 2017).”
HDACs and HDAC Inhibitors in Cancer Development and Therapy (2016, positive): “SIRT6 is rapidly recruited to DNA-damage sites and stimulates DSB repair by mono-ADP-ribosylation of PARP1(Mao et al. 2011).”
DNA damage and its links to neurodegeneration (2014, neutral): “Chromatin modifications in the DDR The formation of DNA DSBs triggers various chromatin modifications, including polyADP-ribosylation mediated by PARP1; histone acetylation/deacetylation mediated by HAT such as p300, MOF and TIP60, and HDAC, such as HDAC1, SIRT1 and SIRT6; and ATMdependent H2AX phos”