Open AccessGlobal genomic instability caused by reduced expression of DNA polymerase ε in yeast
Author(s) -
Ke Zhang,
Yan-Fang Sui,
Wu-Long Li,
Gen Chen,
Ximei Wu,
Robert J. Kokoska,
Thomas D. Petes,
Dao-Qiong Zheng
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2119588119
Subject(s) - genome instability , dna polymerase , biology , genetics , dna replication , dna polymerase ii , mitotic crossover , polymerase , gene , dna , microbiology and biotechnology , mutation , dna damage , polymerase chain reaction , reverse transcriptase
Significance Although 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.