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Critical functions of Rpa3/Ssb3 in S-phase DNA damage responses in fission yeast

Academic Article
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Overview

authors

  • Cavero, S.
  • Limbo, O.
  • Russell, Paul

publication date

  • 2010

journal

  • PLoS Genetics  Journal

abstract

  • Replication Protein A (RPA) is a heterotrimeric, single-stranded DNA (ssDNA)-binding complex required for DNA replication and repair, homologous recombination, DNA damage checkpoint signaling, and telomere maintenance. Whilst the larger RPA subunits, Rpa1 and Rpa2, have essential interactions with ssDNA, the molecular functions of the smallest subunit Rpa3 are unknown. Here, we investigate the Rpa3 ortholog Ssb3 in Schizosaccharomyces pombe and find that it is dispensable for cell viability, checkpoint signaling, RPA foci formation, and meiosis. However, increased spontaneous Rad11Rpa1 and Rad22Rad52 nuclear foci in ssb3Δ cells indicate genome maintenance defects. Moreover, Ssb3 is required for resistance to genotoxins that disrupt DNA replication. Genetic interaction studies indicate that Ssb3 has a close functional relationship with the Mms1-Mms22 protein complex, which is required for survival after DNA damage in S-phase, and with the mitotic functions of Mus81-Eme1 Holliday junction resolvase that is required for recovery from replication fork collapse. From these studies we propose that Ssb3 plays a critical role in mediating RPA functions that are required for repair or tolerance of DNA lesions in S-phase. Rpa3 orthologs in humans and other species may have a similar function.

subject areas

  • DNA Damage
  • DNA Repair
  • DNA-Binding Proteins
  • Epistasis, Genetic
  • Genes, Fungal
  • Meiosis
  • Microbial Viability
  • Mutagens
  • Mutation
  • Phenotype
  • Protein Transport
  • S Phase
  • Schizosaccharomyces
  • Schizosaccharomyces pombe Proteins
  • Signal Transduction
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Identity

PubMed Central ID

  • PMC2944793

International Standard Serial Number (ISSN)

  • 1553-7390

Digital Object Identifier (DOI)

  • 10.1371/journal.pgen.1001138

PubMed ID

  • 20885790
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Additional Document Info

start page

  • e1001138

volume

  • 6

issue

  • 9

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