Crosstalk between histone modifications during the DNA damage response

Trends Cell Biol. 2009 May;19(5):207-17. doi: 10.1016/j.tcb.2009.03.001. Epub 2009 Apr 1.

Abstract

Chromatin structure has a crucial role in processes of metabolism, including transcription, DNA replication and DNA damage repair. An evolutionarily conserved variant of histone H2A, called H2AX, is one of the key components of chromatin. H2AX becomes rapidly phosphorylated on chromatin surrounding DNA double-strand breaks (DSBs). Recent studies have shown that H2AX and other components of damaged chromatin also become modified by acetylation and ubiquitylation. This review discusses how specific combinations of histone modifications affect the accumulation and function of DNA repair factors (MDC1, RNF8, RNF168, 53BP1, BRCA1) and chromatin remodeling complexes (INO80, SWR1, TIP60-p400) at DSBs. These collectively regulate DSB repair and checkpoint arrest, avoiding genomic instability and oncogenic transformation in higher eukaryotes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • BRCA1 Protein / metabolism
  • Chromatin / metabolism*
  • DNA Damage / physiology*
  • DNA Repair / physiology*
  • Histone Acetyltransferases / metabolism
  • Histones / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Nuclear Proteins / metabolism
  • Trans-Activators / metabolism
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • BRCA1 Protein
  • Chromatin
  • Histones
  • Intracellular Signaling Peptides and Proteins
  • MDC1 protein, human
  • MDC1 protein, mouse
  • Nuclear Proteins
  • Trans-Activators
  • Ubiquitin
  • Histone Acetyltransferases
  • Ubiquitin-Protein Ligases