期刊
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
卷 737, 期 1-2, 页码 34-42出版社
ELSEVIER
DOI: 10.1016/j.mrfmmm.2012.06.002
关键词
DNA polymerase epsilon (Pol epsilon); DNA polymerase zeta (Pol zeta); Error-prone DNA polymerase; Spontaneous mutagenesis; DNA replication fidelity
资金
- Ministry of Science and Higher Education, Poland [N N301 314437, N N303 566639, N N301 298537]
The Saccharomyces cerevisiae DNA polymerase epsilon holoenzyme (Pol epsilon HE) is composed of four subunits: Pol2p, Dpb2p, Dpb3p and Dpb4p. The biological functions of Pol2p, the catalytic subunit of Pol epsilon, are subject of active investigation, while the role of the other three, noncatalytic subunits, is not well defined. We showed previously that mutations in Dpb2p, a noncatalytic but essential subunit of Pol epsilon HE, influence the fidelity of DNA replication in yeast cells. The strength of the mutator phenotype due to the different dpb2 alleles was inversely proportional to the strength of protein-protein interactions between Pol2p and the mutated forms of Dpb2p. To understand better the mechanisms of the contribution of Dpb2p to the controlling of the level of spontaneous mutagenesis we undertook here a further genetic analysis of the mutator phenotype observed in dpb2 mutants. We demonstrate that the presence of mutated forms of Dpb2p in the cell not only influences the intrinsic fidelity of Pol epsilon but also facilitates more frequent participation of error-prone DNA polymerase zeta (Pol zeta) in DNA replication. The obtained results suggest that the structural integrity of Pol epsilon HE is a crucial contributor to accurate chromosomal DNA replication and, when compromised, favors participation of error prone DNA Pol zeta in this process. (C) 2012 Elsevier B.V. All rights reserved.
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