DNA polymerases at the eukaryotic replication fork thirty years after: Connection to cancer

Youri I. Pavlov, Anna S. Zhuk, Elena I. Stepchenkova

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

Recent studies on tumor genomes revealed that mutations in genes of replicative DNA polymerases cause a predisposition for cancer by increasing genome instability. The past 10 years have uncovered exciting details about the structure and function of replicative DNA polymerases and the replication fork organization. The principal idea of participation of different polymerases in specific transactions at the fork proposed by Morrison and coauthors 30 years ago and later named “division of labor,” remains standing, with an amendment of the broader role of polymerase δ in the replication of both the lagging and leading DNA strands. However, cancer-associated mutations predominantly affect the catalytic subunit of polymerase ε that participates in leading strand DNA synthesis. We analyze how new findings in the DNA replication field help elucidate the polymerase variants’ effects on cancer.

Original languageEnglish (US)
Article number3489
Pages (from-to)1-21
Number of pages21
JournalCancers
Volume12
Issue number12
DOIs
StatePublished - Dec 2020

Keywords

  • Cancer predisposition
  • DNA polymerases
  • Mutation rates
  • Proofreading exonucleases
  • Replication fidelity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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