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Reference - PMID:17178839 - Fission yeast Cut8 is required for the repair of DNA double-strand breaks, ribosomal DNA maintenance, and cell survival in the absence of Rqh1 helicase.

Reference summary

PubMed ID
PMID:17178839
Title
Fission yeast Cut8 is required for the repair of DNA double-strand breaks, ribosomal DNA maintenance, and cell survival in the absence of Rqh1 helicase.
Authors
Kearsey SE, Stevenson AL, Toda T, Wang SW
Citation
Mol Cell Biol 2007 Mar;27(5):1558-67
Publication year
2007
Abstract
Schizosaccharomyces pombe Rqh1 is a member of the RecQ DNA helicase family. Members of this protein family are mutated in cancer predisposition diseases, causing Bloom's, Werner, and Rothmund-Thomson syndromes. Rqh1 forms a complex with topoisomerase III and is proposed to process or disrupt aberrant recombination structures that arise during S phase to allow proper chromosome segregation during mitosis. Intriguingly, in the absence of Rqh1, processing of these structures appears to be dependent on Rad3 (human ATR) in a manner that is distinct from its role in checkpoint control. Here, we show that rad3 rqh1 mutants are normally committed to a lethal pathway of DNA repair requiring homologous recombination, but blocking this pathway by Rhp51 inactivation restores viability. Remarkably, viability is also restored by overexpression of Cut8, a nuclear envelope protein involved in tethering and proper function of the proteasome. In keeping with a recently described function of the proteasome in the repair of DNA double-strand breaks, we found that Cut8 is also required for DNA double-strand break repair and is essential for proper chromosome segregation in the absence of Rqh1, suggesting that these proteins might function in a common pathway in homologous recombination repair to ensure accurate nuclear division in S. pombe.

Annotation

Multi-locus phenotype

FYPO:0003165 - cut with abnormal chromosome segregation

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

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FYPO:0005435 - inviable after spore germination with elongated germ tube and fragmented nucleus

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FYPO:0002061 - inviable vegetative cell population

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FYPO:0001234 - slow vegetative cell population growth

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FYPO:0002058 - viable cell population

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FYPO:0002060 - viable vegetative cell population

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Single locus phenotype

FYPO:0000671 - abnormal rDNA separation

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FYPO:0005436 - abolished double-strand break repair

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FYPO:0000950 - elongated aseptate vegetative cell

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FYPO:0002061 - inviable vegetative cell population

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FYPO:0001705 - normal mitotic DNA damage checkpoint

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FYPO:0005437 - normal number of Rad52 foci during cellular response to bleomycin

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FYPO:0000095 - sensitive to bleomycin

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FYPO:0000088 - sensitive to hydroxyurea

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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:0002060 - viable vegetative cell population

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