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Reference - PMID:20885790 - Critical functions of Rpa3/Ssb3 in S-phase DNA damage responses in fission yeast.

Reference summary

PubMed ID
PMID:20885790
Title
Critical functions of Rpa3/Ssb3 in S-phase DNA damage responses in fission yeast.
Authors
Cavero S, Limbo O, Russell P
Citation
PLoS Genet 2010 Sep 23;6(9):e1001138
Publication year
2010
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.

Annotation

GO cellular component

GO:0035861 - site of double-strand break

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Multi-locus phenotype

FYPO:0001355 - decreased vegetative cell population growth

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FYPO:0002262 - inviable after spore germination, multiple cell divisions, elongated cell

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FYPO:0002061 - inviable vegetative cell population

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FYPO:0001315 - normal vegetative cell morphology

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FYPO:0000085 - sensitive to camptothecin

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FYPO:0000088 - sensitive to hydroxyurea

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FYPO:0000267 - sensitive to ionizing radiation during vegetative growth

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FYPO:0000089 - sensitive to methyl methanesulfonate

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FYPO:0000268 - sensitive to UV during vegetative growth

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FYPO:0001492 - viable elongated vegetative cell

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Single locus phenotype

FYPO:0000972 - increased number of Rad52 foci during vegetative growth

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FYPO:0002573 - increased number of Ssb1 foci

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FYPO:0002899 - normal protein phosphorylation during cellular response to DNA damage

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FYPO:0000085 - sensitive to camptothecin

Genes:

Genotypes:

FYPO:0000088 - sensitive to hydroxyurea

Genes:

Genotypes:

FYPO:0000267 - sensitive to ionizing radiation during vegetative growth

Genes:

Genotypes:

FYPO:0000089 - sensitive to methyl methanesulfonate

Genes:

Genotypes:

FYPO:0000268 - sensitive to UV during vegetative growth

Genes:

Genotypes:

FYPO:0001492 - viable elongated vegetative cell

Genes:

Genotypes: