Regulation of oxidized base damage repair by chromatin assembly factor 1 subunit A

Nucleic Acids Res. 2017 Jan 25;45(2):739-748. doi: 10.1093/nar/gkw1024. Epub 2016 Oct 27.


Reactive oxygen species (ROS), generated both endogenously and in response to exogenous stress, induce point mutations by mis-replication of oxidized bases and other lesions in the genome. Repair of these lesions via base excision repair (BER) pathway maintains genomic fidelity. Regulation of the BER pathway for mutagenic oxidized bases, initiated by NEIL1 and other DNA glycosylases at the chromatin level remains unexplored. Whether single nucleotide (SN)-BER of a damaged base requires histone deposition or nucleosome remodeling is unknown, unlike nucleosome reassembly which is shown to be required for other DNA repair processes. Here we show that chromatin assembly factor (CAF)-1 subunit A (CHAF1A), the p150 subunit of the histone H3/H4 chaperone, and its partner anti-silencing function protein 1A (ASF1A), which we identified in human NEIL1 immunoprecipitation complex, transiently dissociate from chromatin bound NEIL1 complex in G1 cells after induction of oxidative base damage. CHAF1A inhibits NEIL1 initiated repair in vitro Subsequent restoration of the chaperone-BER complex in cell, presumably after completion of repair, suggests that histone chaperones sequester the repair complex for oxidized bases in non-replicating chromatin, and allow repair when oxidized bases are induced in the genome.

MeSH terms

  • Cell Line
  • Chromatin / genetics
  • Chromatin / metabolism
  • Chromatin Assembly Factor-1 / metabolism*
  • DNA Damage* / radiation effects
  • DNA Glycosylases / metabolism
  • DNA Repair*
  • Glucose Oxidase / metabolism
  • Histones / metabolism
  • Humans
  • Molecular Chaperones / metabolism
  • Multiprotein Complexes
  • Oxidation-Reduction*
  • Oxidative Stress*
  • Protein Binding
  • Radiation, Ionizing
  • Reactive Oxygen Species
  • Transcription Factors


  • CNOT8 protein, human
  • Chromatin
  • Chromatin Assembly Factor-1
  • Histones
  • Molecular Chaperones
  • Multiprotein Complexes
  • Reactive Oxygen Species
  • Transcription Factors
  • Glucose Oxidase
  • DNA Glycosylases
  • NEIL1 protein, human