RRC ID 47466
Author Zhang JM, Liu XM, Ding YH, Xiong LY, Ren JY, Zhou ZX, Wang HT, Zhang MJ, Yu Y, Dong MQ, Du LL.
Title Fission yeast Pxd1 promotes proper DNA repair by activating Rad16XPF and inhibiting Dna2.
Journal PLoS Biol
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.
Volume 12(9)
Pages e1001946
Published 2014-9-1
DOI 10.1371/journal.pbio.1001946
PMID 25203555
PMC PMC4159138
MeSH Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism DNA Damage DNA Helicases / genetics DNA Helicases / metabolism DNA Repair* DNA Topoisomerases, Type I / genetics DNA Topoisomerases, Type I / metabolism DNA, Fungal / genetics* DNA, Fungal / metabolism DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Flap Endonucleases / antagonists & inhibitors Flap Endonucleases / genetics* Flap Endonucleases / metabolism Gene Expression Regulation, Fungal* Protein Binding Schizosaccharomyces / enzymology Schizosaccharomyces / genetics* Schizosaccharomyces pombe Proteins / agonists Schizosaccharomyces pombe Proteins / antagonists & inhibitors Schizosaccharomyces pombe Proteins / genetics* Schizosaccharomyces pombe Proteins / metabolism Signal Transduction
IF 7.076
Times Cited 9
DNA material S. pombe ORFeome clone SpYFH33E03 (SPW093299) SpYFH34B04 (SPW093628) SpYFH47F11 (SPW098931).