The dark side of the ring: role of the DNA sliding surface of PCNA

Matteo De March, Alfredo De Biasio

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The proliferating cell nuclear antigen (PCNA) sliding clamp lies at the heart of the accurate duplication of eukaryotic genomes. While the outer surface of the PCNA ring interacts with polymerases and other factors, the role of the inner wall facing the DNA is elusive. Recent evidence shows that conserved basic residues in the PCNA central channel create a specific surface that recognizes the DNA backbone and enables the clamp to slide by rotationally tracking the DNA helix. The sliding surface can be modulated (i) through lysine acetylation, which triggers PCNA degradation during nucleotide excision repair (NER) and stimulates repair by homologous recombination (HR) or (ii) through binding of the protein factor p15PAF, which turns off DNA lesion bypass. Thus, the inner surface of PCNA is unexpectedly highly regulated to control resistance to DNA damage. From a structural viewpoint, we reflect on these findings that open a new perspective on PCNA function and offer opportunities to develop tools to manipulate the DNA damage response in cancer treatment.
Original languageEnglish (US)
Pages (from-to)663-673
Number of pages11
JournalCritical Reviews in Biochemistry and Molecular Biology
Volume52
Issue number6
DOIs
StatePublished - Nov 2 2017
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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