Global genomic instability caused by reduced expression of DNA polymerase ε in yeast
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 15, 2022
- Source ID
- 10.1073/pnas.2119588119
Entities
People
- Dao-qiong Zheng
- Gen Chen
- Ke Zhang
- Robert J. Kokoska
- Thomas D. Petes
- Wu-long Li
- Xue-chang Wu
- Yang Sui
Organizations
- Army Research Office
- Duke University
- National Institute of General Medical Sciences
- National Natural Science Foundation of China
- Zhejiang University