Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 7925-7942 |
| Number of pages | 18 |
| Journal | Cellular and Molecular Life Sciences |
| Volume | 78 |
| Issue number | 24 |
| DOIs | |
| Publication status | Published - 3 Nov 2021 |
Bibliographical note
Funding Information:MSL was supported by an ENW-M (OCENW.KLEIN.090) and ALW-VIDI grants (ALW.016.161.320) from the Dutch Research Council (NWO). HL is funded by CancerGenomiCs.nl and the Oncode Institute, which is partly financed by the Dutch Cancer Society. ODS was supported by the Korean Institute of Basic Science (IBS-R022-A1) and the US National Cancer Institute (P01-CA092584, R01CA218315).
Publisher Copyright:
© 2021, The Author(s).