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The Histone Chaperone FACT Coordinates H2A.X-Dependent Signaling and Repair of DNA Damage

Sandra Piquet1, Florent Le Parc1, Siau-Kun Bai1

  • 1Epigenome Integrity Group, Epigenetics & Cell Fate Centre, UMR7216 CNRS, Paris Diderot University, Sorbonne Paris Cité, 75013 Paris, France.

Molecular Cell
|October 23, 2018
PubMed

Insights

DNA damage repair involves coordinating signaling and chromatin maintenance. New histone variant H2A.X is deposited at damage sites via the FACT chaperone, enhancing DNA damage signaling during repair.

Area of Science:

  • Cellular biology
  • Molecular biology
  • Genetics

Background:

  • Cellular function and identity rely on coordinated DNA damage response and chromatin maintenance.
  • Mechanisms linking DNA damage signaling, repair, and chromatin integrity are not fully understood.

Purpose of the Study:

  • Investigate mechanisms of histone variant H2A.X distribution in mammalian chromatin during DNA damage response.
  • Elucidate the role of histone chaperones in H2A.X dynamics and DNA damage signaling.

Main Methods:

  • Studied H2A.X and H2A.Z variant distribution in mammalian chromatin after genotoxic stress.
  • Identified histone chaperone FACT's role in H2A.X deposition.
  • Assessed FACT's functional impact on H2A.X-dependent DNA damage signaling.

Main Results:

  • H2A.X is deposited de novo at DNA damage sites in a repair-dependent manner.
  • H2A.Z is evicted from DNA damage sites, altering the chromatin landscape.
  • The histone chaperone FACT facilitates new H2A.X deposition and potentiates DNA damage signaling.

Conclusions:

  • FACT mediates H2A.X deposition, crucial for DNA damage signaling.
  • Dynamic H2A.X deposition shapes chromatin at repair sites, reflecting DNA damage.
  • This process may tailor DNA damage signaling to repair progression.
Keywords:
ANP32EDNA damage signalingDNA repairFACTH2A.XH2A.ZUV damagechromatinhistone chaperoneshistone variants

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