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

Crit Rev Biochem Mol Biol

a Structural Biology Laboratory , Elettra-Sincrotrone Trieste S.C.p.A , Trieste , Italy.

Published: December 2017

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 p15, 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.

Download full-text PDF

Source
http://dx.doi.org/10.1080/10409238.2017.1364218DOI Listing

Publication Analysis

Top Keywords

surface pcna
12
sliding surface
8
dna damage
8
dna
7
pcna
7
surface
5
dark side
4
side ring
4
ring role
4
role dna
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!