Fission Yeast Pxd1 Promotes Proper DNA Repair by Activating Rad16 XPF and Inhibiting Dna2: e1001946

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...

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Bibliographic Details
Published in:PLoS biology 2014-09, Vol.12 (9)
Main Authors: Zhang, Jia-Min, Liu, Xiao-Man, Ding, Yue-He, Xiong, Liang-Yao, Ren, Jing-Yi, Zhou, Zhi-Xiong, Wang, Hai-Tao, Zhang, Mei-Jun, Yu, Yang, Dong, Meng-Qiu, Du, Li-Lin
Format: Article
Language:English
Subjects:
Annealing
Deoxyribonucleic acid
DNA
DNA repair
Genomes
Mass spectrometry
Mutation
Proteins
Schizosaccharomyces pombe
Scientific imaging
Yeast
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Summary: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.
ISSN:1544-9173
1545-7885
DOI:10.1371/journal.pbio.1001946