Nucleotide excision repair leaves a mark on chromatin: DNA damage detection in nucleosomes

Cell Mol Life Sci. 2021 Dec;78(24):7925-7942. doi: 10.1007/s00018-021-03984-7. Epub 2021 Nov 3.


Global genome nucleotide excision repair (GG-NER) eliminates a broad spectrum of DNA lesions from genomic DNA. Genomic DNA is tightly wrapped around histones creating a barrier for DNA repair proteins to access DNA lesions buried in nucleosomal DNA. The DNA-damage sensors XPC and DDB2 recognize DNA lesions in nucleosomal DNA and initiate repair. The emerging view is that a tight interplay between XPC and DDB2 is regulated by post-translational modifications on the damage sensors themselves as well as on chromatin containing DNA lesions. The choreography between XPC and DDB2, their interconnection with post-translational modifications such as ubiquitylation, SUMOylation, methylation, poly(ADP-ribos)ylation, acetylation, and the functional links with chromatin remodelling activities regulate not only the initial recognition of DNA lesions in nucleosomes, but also the downstream recruitment and necessary displacement of GG-NER factors as repair progresses. In this review, we highlight how nucleotide excision repair leaves a mark on chromatin to enable DNA damage detection in nucleosomes.

Keywords: Chromatin; DDB2; Nucleotide excision repair; PTM; Post-translational modification; XPC.

Publication types

  • Review

MeSH terms

  • Animals
  • Chromatin / chemistry
  • Chromatin / genetics*
  • DNA Damage*
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / metabolism*
  • DNA Repair*
  • Humans
  • Nucleosomes / physiology*
  • Protein Processing, Post-Translational*


  • Chromatin
  • Nucleosomes
  • DNA Repair Enzymes