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Reference - PMID:25203555 - Fission yeast Pxd1 promotes proper DNA repair by activating Rad16XPF and inhibiting Dna2.

Reference summary

PubMed ID
PMID:25203555
Title
Fission yeast Pxd1 promotes proper DNA repair by activating Rad16XPF and inhibiting Dna2.
Authors
Zhang JM, Liu XM, Ding YH, Xiong LY, Ren JY, Zhou ZX, Wang HT, Zhang MJ, Yu Y, Dong MQ, Du LL
Citation
PLoS Biol 2014 Sep;12(9):e1001946
Publication year
2014
Abstract
Structure-specific nucleases play crucial roles in many DNA repair pathways. They must be precisely controlled to ensure optimal repair outcomes; however, mechanisms of their regulation are not fully understood. Here, we report a fission yeast protein, Pxd1, that binds to and regulates two structure-specific nucleases: Rad16XPF-Swi10ERCC1 and Dna2-Cdc24. Strikingly, Pxd1 influences the activities of these two nucleases in opposite ways: It activates the 3' endonuclease activity of Rad16-Swi10 but inhibits the RPA-mediated activation of the 5' endonuclease activity of Dna2. Pxd1 is required for Rad16-Swi10 to function in single-strand annealing, mating-type switching, and the removal of Top1-DNA adducts. Meanwhile, Pxd1 attenuates DNA end resection mediated by the Rqh1-Dna2 pathway. Disabling the Dna2-inhibitory activity of Pxd1 results in enhanced use of a break-distal repeat sequence in single-strand annealing and a greater loss of genetic information. We propose that Pxd1 promotes proper DNA repair by differentially regulating two structure-specific nucleases.

Annotation

GO biological process

GO:0000729 - DNA double-strand break processing

Genes:

GO:0045002 - double-strand break repair via single-strand annealing

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GO:0007534 - gene conversion at mating-type locus

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GO molecular function

GO:1990599 - 3' overhang single-stranded DNA endonuclease activity

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GO:1990601 - 5' overhang single-stranded DNA endonuclease activity

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GO:0140656 - endodeoxyribonuclease activator activity

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GO:0005515 - protein binding

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Multi-locus phenotype

FYPO:0001357 - normal vegetative cell population growth

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Genotypes:

FYPO:0000267 - sensitive to ionizing radiation during vegetative growth

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Genotypes:

FYPO:0002060 - viable vegetative cell population

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Single locus phenotype

FYPO:0002553 - abnormal double-strand break processing

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Genotypes:

FYPO:0000777 - abnormal double-strand break repair during vegetative growth

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Genotypes:

FYPO:0003164 - abolished nuclease activity

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FYPO:0000705 - abolished protein-protein interaction

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FYPO:0000470 - decreased mating type switching

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FYPO:0004253 - decreased nuclease activity

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FYPO:0001645 - decreased protein-protein interaction

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Genotypes:

FYPO:0001355 - decreased vegetative cell population growth

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FYPO:0002169 - normal growth during cellular response to gamma radiation

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FYPO:0000969 - normal growth during cellular response to UV

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FYPO:0001690 - normal growth on camptothecin

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FYPO:0001164 - normal growth on glucose carbon source

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FYPO:0000963 - normal growth on hydroxyurea

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Genotypes:

FYPO:0000957 - normal growth on methyl methanesulfonate

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Genotypes:

FYPO:0000085 - sensitive to camptothecin

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Genotypes:

FYPO:0000088 - sensitive to hydroxyurea

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Genotypes:

FYPO:0000267 - sensitive to ionizing radiation during vegetative growth

Genes:

Genotypes:

FYPO:0000089 - sensitive to methyl methanesulfonate

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Genotypes:

FYPO:0000268 - sensitive to UV during vegetative growth

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Genotypes:

FYPO:0002177 - viable vegetative cell with normal cell morphology

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