Mechanisms of DNA damage tolerance

post-translational regulation of PCNA

Wendy Leung, Ryan M. Baxley, George-Lucian Moldovan, Anja Katrin Bielinsky

Research output: Contribution to journalReview article

5 Citations (Scopus)

Abstract

DNA damage is a constant source of stress challenging genomic integrity. To ensure faithful duplication of our genomes, mechanisms have evolved to deal with damage encountered during replication. One such mechanism is referred to as DNA damage tolerance (DDT). DDT allows for replication to continue in the presence of a DNA lesion by promoting damage bypass. Two major DDT pathways exist: error-prone translesion synthesis (TLS) and error-free template switching (TS). TLS recruits low-fidelity DNA polymerases to directly replicate across the damaged template, whereas TS uses the nascent sister chromatid as a template for bypass. Both pathways must be tightly controlled to prevent the accumulation of mutations that can occur from the dysregulation of DDT proteins. A key regulator of error-prone versus error-free DDT is the replication clamp, proliferating cell nuclear antigen (PCNA). Post-translational modifications (PTMs) of PCNA, mainly by ubiquitin and SUMO (small ubiquitin-like modifier), play a critical role in DDT. In this review, we will discuss the different types of PTMs of PCNA and how they regulate DDT in response to replication stress. We will also cover the roles of PCNA PTMs in lagging strand synthesis, meiotic recombination, as well as somatic hypermutation and class switch recombination.

Original languageEnglish (US)
Article number10
JournalGenes
Volume10
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

Proliferating Cell Nuclear Antigen
DNA Damage
Post Translational Protein Processing
Ubiquitin
Genetic Recombination
Chromatids
DNA-Directed DNA Polymerase
Genome
DNA

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Leung, Wendy ; Baxley, Ryan M. ; Moldovan, George-Lucian ; Bielinsky, Anja Katrin. / Mechanisms of DNA damage tolerance : post-translational regulation of PCNA. In: Genes. 2019 ; Vol. 10, No. 1.
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Mechanisms of DNA damage tolerance : post-translational regulation of PCNA. / Leung, Wendy; Baxley, Ryan M.; Moldovan, George-Lucian; Bielinsky, Anja Katrin.

In: Genes, Vol. 10, No. 1, 10, 01.01.2019.

Research output: Contribution to journalReview article

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