Mutations at the Subunit Interface of Yeast Proliferating Cell Nuclear Antigen Reveal a Versatile Regulatory Domain
Proliferating cell nuclear antigen (PCNA) plays a key role in many cellular processes and due to that it interacts with a plethora of proteins. The main interacting surfaces of Saccharomyces cerevisiae PCNA have been mapped to the interdomain connecting loop and to the carboxy-terminal domain. Here...
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Published in | PloS one Vol. 11; no. 8; p. e0161307 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
18.08.2016
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | Proliferating cell nuclear antigen (PCNA) plays a key role in many cellular processes and due to that it interacts with a plethora of proteins. The main interacting surfaces of Saccharomyces cerevisiae PCNA have been mapped to the interdomain connecting loop and to the carboxy-terminal domain. Here we report that the subunit interface of yeast PCNA also has regulatory roles in the function of several DNA damage response pathways. Using site-directed mutagenesis we engineered mutations at both sides of the interface and investigated the effect of these alleles on DNA damage response. Genetic experiments with strains bearing the mutant alleles revealed that mutagenic translesion synthesis, nucleotide excision repair, and homologous recombination are all regulated through residues at the subunit interface. Moreover, genetic characterization of one of our mutants identifies a new sub-branch of nucleotide excision repair. Based on these results we conclude that residues at the subunit boundary of PCNA are not only important for the formation of the trimer structure of PCNA, but they constitute a regulatory protein domain that mediates different DNA damage response pathways, as well. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interests: The authors have declared that no competing interests exist. Current address: Institute of Medical Sciences Foresterhill, University of Aberdeen, Aberdeen, United Kingdom Conceptualization: IU.Formal analysis: ZS EB.Funding acquisition: IU.Investigation: MH OF ZS AD VKG EB IU.Methodology: MH IU.Project administration: IU.Supervision: IU.Validation: MH IU.Visualization: MH.Writing - original draft: IU.Writing - review & editing: MH EB IU. |
ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0161307 |