Mutations at the Subunit Interface of Yeast Proliferating Cell Nuclear Antigen Reveal a Versatile Regulatory Domain
| Autor: | Andrea Daraba, Ildiko Unk, Miklós Halmai, Orsolya Frittmann, Vamsi K. Gali, Eva Balint, Zoltán Szabó |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Saccharomyces cerevisiae Proteins DNA Repair Transcription Genetic Light DNA repair DNA damage lcsh:Medicine Saccharomyces cerevisiae DNA replication Biology medicine.disease_cause Biochemistry RFC2 03 medical and health sciences 0302 clinical medicine Proliferating Cell Nuclear Antigen Ultraviolet Radiation Genetics medicine lcsh:Science Mutation Multidisciplinary Biology and life sciences Physics Electromagnetic Radiation lcsh:R Mutagenesis Organisms Fungi DNA Molecular biology Yeast Cell biology Proliferating cell nuclear antigen Nucleic acids Mutant Strains 030104 developmental biology Physical Sciences Mutagenesis Site-Directed biology.protein lcsh:Q Homologous recombination 030217 neurology & neurosurgery Research Article Nucleotide excision repair |
| Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 8, p e0161307 (2016) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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