Global Genomic Instability Caused by Reduced Expression of DNA Polymerase ε in Yeast

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2022 Mar 15

PMID 35290114

Authors

Ke Zhang

Yang Sui

Wu-Long Li

Gen Chen

Xue-Chang Wu

Robert J Kokoska

Thomas D Petes

Dao-Qiong Zheng

Affiliations

Soon will be listed here.

Abstract

SignificanceAlthough most studies of the genetic regulation of genome stability involve an analysis of mutations within the coding sequences of genes required for DNA replication or DNA repair, recent studies in yeast show that reduced levels of wild-type enzymes can also produce a mutator phenotype. By whole-genome sequencing and other methods, we find that reduced levels of the wild-type DNA polymerase ε in yeast greatly increase the rates of mitotic recombination, aneuploidy, and single-base mutations. The observed pattern of genome instability is different from those observed in yeast strains with reduced levels of the other replicative DNA polymerases, Pol α and Pol δ. These observations are relevant to our understanding of cancer and other diseases associated with genetic instability.

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