Control of DNA Damage Bypass by Ubiquitylation of PCNA.

Abstract:

:DNA damage leads to genome instability by interfering with DNA replication. Cells possess several damage bypass pathways that mitigate the effects of DNA damage during replication. These pathways include translesion synthesis and template switching. These pathways are regulated largely through post-translational modifications of proliferating cell nuclear antigen (PCNA), an essential replication accessory factor. Mono-ubiquitylation of PCNA promotes translesion synthesis, and K63-linked poly-ubiquitylation promotes template switching. This article will discuss the mechanisms of how these post-translational modifications of PCNA control these bypass pathways from a structural and biochemical perspective. We will focus on the structure and function of the E3 ubiquitin ligases Rad18 and Rad5 that facilitate the mono-ubiquitylation and poly-ubiquitylation of PCNA, respectively. We conclude by reviewing alternative ideas about how these post-translational modifications of PCNA regulate the assembly of the multi-protein complexes that promote damage bypass pathways.

journal_name

Genes (Basel)

journal_title

Genes

authors

Ripley BM,Gildenberg MS,Washington MT

doi

10.3390/genes11020138

subject

Has Abstract

pub_date

2020-01-29 00:00:00

issue

2

issn

2073-4425

pii

genes11020138

journal_volume

11

pub_type

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