SIRT6 is a DNA double-strand break sensor - Archive ouverte HAL
Article Dans Une Revue eLife Année : 2020

SIRT6 is a DNA double-strand break sensor

Lior Onn
  • Fonction : Auteur
Miguel Portillo
  • Fonction : Auteur
Gal Cleitman
  • Fonction : Auteur
Shai Kaluski
  • Fonction : Auteur
Ido Shirat
  • Fonction : Auteur
Zeev Slobodnik
  • Fonction : Auteur
Monica Einav
  • Fonction : Auteur
Barak Akabayov
Debra Toiber

Résumé

DNA double-strand breaks (DSB) are the most deleterious type of DNA damage. In this work, we show that SIRT6 directly recognizes DNA damage through a tunnel-like structure that has high affinity for DSB. SIRT6 relocates to sites of damage independently of signaling and known sensors. It activates downstream signaling for DSB repair by triggering ATM recruitment, H2AX phosphorylation and the recruitment of proteins of the homologous recombination and non-homologous end joining pathways. Our findings indicate that SIRT6 plays a previously uncharacterized role as a DNA damage sensor, a critical factor in initiating the DNA damage response (DDR). Moreover, other Sirtuins share some DSB-binding capacity and DDR activation. SIRT6 activates the DDR before the repair pathway is chosen, and prevents genomic instability. Our findings place SIRT6 as a sensor of DSB, and pave the road to dissecting the contributions of distinct DSB sensors in downstream signaling.

Dates et versions

hal-04689152 , version 1 (05-09-2024)

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Citer

Lior Onn, Miguel Portillo, Stefan Ilic, Gal Cleitman, Daniel Stein, et al.. SIRT6 is a DNA double-strand break sensor. eLife, 2020, 9, ⟨10.7554/eLife.51636⟩. ⟨hal-04689152⟩
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