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Reference - PMID:12944482 - The fission yeast Rad32 (Mre11)-Rad50-Nbs1 complex is required for the S-phase DNA damage checkpoint.

Reference summary

PubMed ID
PMID:12944482
Title
The fission yeast Rad32 (Mre11)-Rad50-Nbs1 complex is required for the S-phase DNA damage checkpoint.
Authors
Chahwan C, Nakamura TM, Sivakumar S, Russell P, Rhind N
Citation
Mol Cell Biol 2003 Sep;23(18):6564-73
Publication year
2003
Abstract
Mre11, Rad50, and Nbs1 form a conserved heterotrimeric complex that is involved in recombination and DNA damage checkpoints. Mutations in this complex disrupt the S-phase DNA damage checkpoint, the checkpoint which slows replication in response to DNA damage, and cause chromosome instability and cancer in humans. However, how these proteins function and specifically where they act in the checkpoint signaling pathway remain crucial questions. We identified fission yeast Nbs1 by using a comparative genomic approach and showed that the genes for human Nbs1 and fission yeast Nbs1 and that for their budding yeast counterpart, Xrs2, are members of an evolutionarily related but rapidly diverging gene family. Fission yeast Nbs1, Rad32 (the homolog of Mre11), and Rad50 are involved in DNA damage repair, telomere regulation, and the S-phase DNA damage checkpoint. However, they are not required for G(2) DNA damage checkpoint. Our results suggest that a complex of Rad32, Rad50, and Nbs1 acts specifically in the S-phase branch of the DNA damage checkpoint and is not involved in general DNA damage recognition or signaling.

Annotation

GO biological process

GO:0000724 - double-strand break repair via homologous recombination

Genes:

GO:0031573 - mitotic intra-S DNA damage checkpoint signaling

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GO:0000723 - telomere maintenance

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GO cellular component

GO:0030870 - Mre11 complex

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GO:0005634 - nucleus

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Multi-locus phenotype

FYPO:0002702 - circularized chromosome

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Genotypes:

FYPO:0002687 - normal telomere length during vegetative growth

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Genotypes:

FYPO:0000267 - sensitive to ionizing radiation during vegetative growth

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Genotypes:

FYPO:0000089 - sensitive to methyl methanesulfonate

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Genotypes:

FYPO:0001234 - slow vegetative cell population growth

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Protein features

PBO:0111779 - BRCT domain

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Single locus phenotype

FYPO:0005268 - abnormal mitotic cell cycle regulation during cellular response to methyl methanesulfonate

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Genotypes:

FYPO:0005408 - decreased duration of mitotic S phase during cellular response to methyl methanesulfonate

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Genotypes:

FYPO:0001927 - normal cell cycle regulation during cellular response to ionizing radiation

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Genotypes:

FYPO:0002687 - normal telomere length during vegetative growth

Genes:

Genotypes:

FYPO:0000267 - sensitive to ionizing radiation during vegetative growth

Genes:

Genotypes:

FYPO:0000089 - sensitive to methyl methanesulfonate

Genes:

Genotypes:

FYPO:0002239 - shortened telomeres during vegetative growth

Genes:

Genotypes:

FYPO:0001234 - slow vegetative cell population growth

Genes:

Genotypes: