Real-Time Tracking of Parental Histones Reveals Their Contribution to Chromatin Integrity Following DNA Damage

Mol Cell. 2016 Oct 6;64(1):65-78. doi: 10.1016/j.molcel.2016.08.019. Epub 2016 Sep 15.

Abstract

Chromatin integrity is critical for cell function and identity but is challenged by DNA damage. To understand how chromatin architecture and the information that it conveys are preserved or altered following genotoxic stress, we established a system for real-time tracking of parental histones, which characterize the pre-damage chromatin state. Focusing on histone H3 dynamics after local UVC irradiation in human cells, we demonstrate that parental histones rapidly redistribute around damaged regions by a dual mechanism combining chromatin opening and histone mobilization on chromatin. Importantly, parental histones almost entirely recover and mix with new histones in repairing chromatin. Our data further define a close coordination of parental histone dynamics with DNA repair progression through the damage sensor DDB2 (DNA damage-binding protein 2). We speculate that this mechanism may contribute to maintaining a memory of the original chromatin landscape and may help preserve epigenome stability in response to DNA damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Chromatin / chemistry
  • Chromatin / metabolism
  • Chromatin / radiation effects*
  • Chromatin Assembly and Disassembly
  • DNA Damage
  • DNA Repair*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Fluorescent Antibody Technique / methods*
  • Genomic Instability
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Histones / antagonists & inhibitors
  • Histones / genetics*
  • Histones / metabolism
  • Humans
  • Osteoblasts / cytology
  • Osteoblasts / metabolism
  • Osteoblasts / radiation effects*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Ultraviolet Rays

Substances

  • Chromatin
  • DDB2 protein, human
  • DNA-Binding Proteins
  • Histones
  • RNA, Small Interfering
  • Recombinant Fusion Proteins
  • Green Fluorescent Proteins
  • XPC protein, human