Comprehensive mutational analysis of the checkpoint signaling function of Rpa1/Ssb1 in fission yeast.
Journal
PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
04
03
2023
accepted:
24
04
2023
revised:
31
05
2023
medline:
2
6
2023
pubmed:
18
5
2023
entrez:
18
5
2023
Statut:
epublish
Résumé
Replication protein A (RPA) is a heterotrimeric complex and the major single-strand DNA (ssDNA) binding protein in eukaryotes. It plays important roles in DNA replication, repair, recombination, telomere maintenance, and checkpoint signaling. Because RPA is essential for cell survival, understanding its checkpoint signaling function in cells has been challenging. Several RPA mutants have been reported previously in fission yeast. None of them, however, has a defined checkpoint defect. A separation-of-function mutant of RPA, if identified, would provide significant insights into the checkpoint initiation mechanisms. We have explored this possibility and carried out an extensive genetic screen for Rpa1/Ssb1, the large subunit of RPA in fission yeast, looking for mutants with defects in checkpoint signaling. This screen has identified twenty-five primary mutants that are sensitive to genotoxins. Among these mutants, two have been confirmed partially defective in checkpoint signaling primarily at the replication fork, not the DNA damage site. The remaining mutants are likely defective in other functions such as DNA repair or telomere maintenance. Our screened mutants, therefore, provide a valuable tool for future dissection of the multiple functions of RPA in fission yeast.
Identifiants
pubmed: 37200372
doi: 10.1371/journal.pgen.1010691
pii: PGENETICS-D-23-00250
pmc: PMC10231789
doi:
Substances chimiques
DNA-Binding Proteins
0
Replication Protein A
0
DNA, Single-Stranded
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1010691Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM143316
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM144307
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
Copyright: © 2023 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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