Timely upstream events regulating nucleotide excision repair by ubiquitin-proteasome system: ubiquitin guides the way.

The ubiquitin-proteasome system (UPS) plays crucial roles in regulation of multiple DNA repair pathways, including nucleotide excision repair (NER), which eliminates a broad variety of helix-distorting DNA lesions that can otherwise cause deleterious mutations and genomic instability. In mammalian NER, DNA damage sensors, DDB and XPC acting in global genomic NER (GG-NER), and, CSB and RNAPII acting in transcription-coupled NER (TC-NER) sub-pathways, undergo an array of post-translational ubiquitination at the DNA lesion sites. Accumulating evidence indicates that ubiquitination orchestrates the productive assembly of NER preincision complex by driving well-timed compositional changes in DNA damage-assembled sensor complexes. Conversely, the deubiquitination is also intimately involved in regulating the damage sensing aftermath, via removal of degradative ubiquitin modification on XPC and CSB to prevent their proteolysis for the factor recycling. This review summaries the relevant research efforts and latest findings in our understanding of ubiquitin-mediated regulation of NER and active participation by new regulators of NER, e.g., Cullin-Ring ubiquitin ligases (CRLs), ubiquitin-specific proteases (USPs) and ubiquitin-dependent segregase, valosin-containing protein (VCP)/p97. We project hypothetical step-by-step models in which VCP/p97-mediated timely extraction of damage sensors is integral to overall productive NER. The USPs and proteasome subtly counteract in fine-tuning the vital stability and function of NER damage sensors.

• Publication year

  2021

• Venue

  DNA Repair

• Publication date

  2021-05-12

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.dnarep.2021.103128PMID 33991872PMCID PMC8206018
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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