Defective interaction between Pol2p and Dpb2p, subunits of DNA polymerase epsilon, contributes to a mutator phenotype in Saccharomyces cerevisiae
Abstract
Most of the prokaryotic and eukaryotic replicative polymerases are multi-subunit complexes. There are several examples indicating that noncatalytic subunits of DNA polymerases may function as fidelity factors during replication process. In this work, we have further investigated the role of Dpb2p, a noncatalytic subunit of DNA polymerase epsilon holoenzyme from Saccharomyces cerevisiae in controlling the level of spontaneous mutagenesis. The data presented indicate that impaired interaction between catalytic Pol2p subunit and Dpb2p is responsible for the observed mutator phenotype in S. cerevisiae strains carrying different mutated alleles of the DPB2 gene. We observed a significant correlation between the decreased level of interaction between different mutated forms of Dpb2p towards a wild-type form of Pol2p and the strength of mutator phenotype that they confer. We propose that structural integrity of the Pol epsilon holoenzyme is essential for genetic stability in S. cerevisiae cells.
Additional Information
© 2009 Elsevier B.V. Received 24 October 2008; revised 12 March 2009; accepted 17 April 2009. Available online 20 May 2009. We thank Dr. Zygmunt Cie´sla of the Institute of Biochemistry and Biophysics PAS (Warsaw, Poland) for critical reading of the manuscript, Dr. Pawel Siedlecki (Institute of Biochemistry and Biophysics, PAS, Warsaw, Poland) for his efforts in modeling the Dpb2p structure, and Dr. Hiroyuki Araki (Division of Microbial Genetics, National Institute of Genetics, Research Organization of Information and Systems, Shizuoka, Japan) for providing anti-Dpb2p antibodies. We thank also Dr. Thomas L. Mason (Department of Biochemistry, University of Massachusetts, Amherst, MA) for anti-Hts1p antibody. This work was supported by grant 2P04A05126 from the Polish Ministry of Science and Higher Education to M.J., K.F., P.J. and I.J.F; and by U.S. Public Health Service grant TW006463 [Fogarty International Collaboration Award (FIRCA)] to I.J.F., P.J. and J.L.C. K.F. research was additionally supported by grant N302 051 32/3925 from the Polish Ministry of Science and Higher Education.Additional details
- Eprint ID
- 16681
- DOI
- 10.1016/j.mrfmmm.2009.04.012
- Resolver ID
- CaltechAUTHORS:20091112-101049897
- 2P04A05126
- Polish Ministry of Science and Higher Education
- N302 051 32/3925
- Polish Ministry of Science and Higher Education
- TW006463
- U.S. Public Health Service
- Created
-
2009-11-24Created from EPrint's datestamp field
- Updated
-
2021-11-08Created from EPrint's last_modified field