title: Mutations at the Subunit Interface of Yeast Proliferating Cell Nuclear Antigen Reveal a Versatile Regulatory Domain.
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.
authors.affiliation: The Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Miklos
authors.initials: M
authors.lastname: Halmai
authors.affiliation: The Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Orsolya
authors.initials: O
authors.lastname: Frittmann
authors.affiliation: The Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Szabo
authors.affiliation: The Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Andreea
authors.initials: A
authors.lastname: Daraba
authors.affiliation: The Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Vamsi K
authors.initials: VK
authors.lastname: Gali
authors.affiliation: The Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Eva
authors.initials: E
authors.lastname: Balint
authors.affiliation: The Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Ildiko
authors.initials: I
authors.lastname: Unk
mesh_terms: D004249:DNA Damage / Q000235:genetics / Q000502:physiology; D004260:DNA Repair / Q000235:genetics / Q000502:physiology; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics / Q000502:physiology; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics* / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic / Q000235:genetics / Q000502:physiology
chemical_list: C546594:POL30 protein, S cerevisiae; D018809:Proliferating Cell Nuclear Antigen; D029701:Saccharomyces cerevisiae Proteins