Phosphorylated HBO1 at UV irradiated sites is essential for nucleotide excision repair

Nat Commun. 2017 Jul 18:8:16102. doi: 10.1038/ncomms16102.

Abstract

HBO1, a histone acetyl transferase, is a co-activator of DNA pre-replication complex formation. We recently reported that HBO1 is phosphorylated by ATM and/or ATR and binds to DDB2 after ultraviolet irradiation. Here, we show that phosphorylated HBO1 at cyclobutane pyrimidine dimer (CPD) sites mediates histone acetylation to facilitate recruitment of XPC at the damaged DNA sites. Furthermore, HBO1 facilitates accumulation of SNF2H and ACF1, an ATP-dependent chromatin remodelling complex, to CPD sites. Depletion of HBO1 inhibited repair of CPDs and sensitized cells to ultraviolet irradiation. However, depletion of HBO1 in cells derived from xeroderma pigmentosum patient complementation groups, XPE, XPC and XPA, did not lead to additional sensitivity towards ultraviolet irradiation. Our findings suggest that HBO1 acts in concert with SNF2H-ACF1 to make the chromosome structure more accessible to canonical nucleotide excision repair factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA Damage
  • DNA Repair*
  • DNA-Binding Proteins / metabolism
  • Histone Acetyltransferases / metabolism*
  • Humans
  • Phosphorylation
  • Pyrimidine Dimers / metabolism
  • Transcription Factors / metabolism
  • Ultraviolet Rays

Substances

  • BAZ1A protein, human
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Pyrimidine Dimers
  • Transcription Factors
  • XPC protein, human
  • Histone Acetyltransferases
  • KAT7 protein, human
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Adenosine Triphosphatases
  • SMARCA5 protein, human