Mutations at the Subunit Interface of Yeast Proliferating Cell Nuclear Antigen Reveal a Versatile Regulatory Domain

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2016 Aug 19

PMID 27537501

Citations 2

Authors

Miklos Halmai

Orsolya Frittmann

Zoltan Szabo

Andreea Daraba

Vamsi K Gali

Eva Balint

Ildiko Unk

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

The inner side of yeast PCNA contributes to genome stability by mediating interactions with Rad18 and the replicative DNA polymerase δ.

Toth R, Halmai M, Gyorfy Z, Balint E, Unk I Sci Rep. 2022; 12(1):5163.

PMID: 35338218 PMC: 8956578. DOI: 10.1038/s41598-022-09208-7.

Proliferating cell nuclear antigen restores the enzymatic activity of a DNA ligase I deficient in DNA binding.

Trasvina-Arenas C, Cardona-Felix C, Azuara-Liceaga E, Diaz-Quezada C, Brieba L FEBS Open Bio. 2017; 7(5):659-674.

PMID: 28469979 PMC: 5407892. DOI: 10.1002/2211-5463.12209.

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