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Related Concept Videos

Fixing Double-strand Breaks02:04

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Related Experiment Video

Updated: Dec 29, 2025

Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy
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SIRT6 is a DNA double-strand break sensor.

Lior Onn1,2, Miguel Portillo1,2, Stefan Ilic3

  • 1Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.

Elife
|January 30, 2020
PubMed
Summary

SIRT6 acts as a direct DNA damage sensor, binding to double-strand breaks (DSB) and initiating the DNA damage response (DDR) to prevent genomic instability.

Keywords:
DNA damageDNA repairDSBSIRT6cell biologyhumansensor

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • DNA double-strand breaks (DSB) represent the most severe form of DNA damage.
  • The DNA damage response (DDR) is crucial for maintaining genomic integrity.

Purpose of the Study:

  • To investigate the role of SIRT6 as a direct DNA damage sensor.
  • To elucidate the mechanism by which SIRT6 initiates the DDR.

Main Methods:

  • Direct binding assays to detect SIRT6 interaction with DSB.
  • Cellular localization studies to track SIRT6 relocation to DNA damage sites.
  • Analysis of downstream signaling events, including ATM recruitment and H2AX phosphorylation.

Main Results:

  • SIRT6 directly recognizes and binds to DSB via a unique tunnel structure.
  • SIRT6 relocates to DNA damage sites independently of known sensors.
  • SIRT6 triggers ATM recruitment and downstream signaling, activating homologous recombination and non-homologous end joining pathways.
  • SIRT6 initiates DDR signaling before repair pathway choice, preventing genomic instability.

Conclusions:

  • SIRT6 functions as a critical DNA damage sensor for DSB.
  • SIRT6 plays a key role in initiating the DDR and maintaining genomic stability.
  • Other Sirtuins may also possess DSB-binding and DDR-activating capabilities.