Modulation of mutagenesis in eukaryotes by DNA replication fork dynamics and quality of nucleotide pools

Irina S.R. Waisertreiger, Victoria G. Liston, Miriam R. Menezes, Hyun Min Kim, Kirill S. Lobachev, Elena I. Stepchenkova, Tahir H. Tahirov, Igor B. Rogozin, Youri I. Pavlov

Research output: Contribution to journalReview articlepeer-review

25 Scopus citations

Abstract

The rate of mutations in eukaryotes depends on a plethora of factors and is not immediately derived from the fidelity of DNA polymerases (Pols). Replication of chromosomes containing the anti-parallel strands of duplex DNA occurs through the copying of leading and lagging strand templates by a trio of Pols α, δ and ε{lunate}, with the assistance of Pol ζ and Y-family Pols at difficult DNA template structures or sites of DNA damage. The parameters of the synthesis at a given location are dictated by the quality and quantity of nucleotides in the pools, replication fork architecture, transcription status, regulation of Pol switches, and structure of chromatin. The result of these transactions is a subject of survey and editing by DNA repair.

Original languageEnglish (US)
Pages (from-to)699-724
Number of pages26
JournalEnvironmental and Molecular Mutagenesis
Volume53
Issue number9
DOIs
StatePublished - Dec 2012

Keywords

  • DNA polymerases
  • Mutagenesis
  • Nucleotide pools
  • Okazaki fragments

ASJC Scopus subject areas

  • Epidemiology
  • Genetics(clinical)
  • Health, Toxicology and Mutagenesis

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