RRC ID 76350
Author Xu YJ, Bhadra S, Mahdi ATA, Dev K, Yurtsever I, Nakamura TM.
Title Comprehensive mutational analysis of the checkpoint signaling function of Rpa1/Ssb1 in fission yeast.
Journal PLoS Genet
Abstract 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.
Volume 19(5)
Pages e1010691
Published 2023-5-1
DOI 10.1371/journal.pgen.1010691
PMID 37200372
PMC PMC10231789
MeSH DNA Damage / genetics DNA Repair / genetics DNA Replication / genetics DNA, Single-Stranded / metabolism DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Replication Protein A / genetics Replication Protein A / metabolism Schizosaccharomyces* / genetics Schizosaccharomyces* / metabolism
IF 5.175
Yeast FY20991