title: Fission yeast Pxd1 promotes proper DNA repair by activating Rad16XPF and inhibiting Dna2.
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.
authors.affiliation: National Institute of Biological Sciences, Beijing, China; Graduate School of Peking Union Medical College, Beijing, China.
authors.forename: Jia-Min
authors.initials: JM
authors.lastname: Zhang
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Xiao-Man
authors.initials: XM
authors.lastname: Liu
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Yue-He
authors.initials: YH
authors.lastname: Ding
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Liang-Yao
authors.initials: LY
authors.lastname: Xiong
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Ren
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Zhi-Xiong
authors.initials: ZX
authors.lastname: Zhou
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Wang
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Mei-Jun
authors.initials: MJ
authors.lastname: Zhang
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Meng-Qiu
authors.initials: MQ
authors.lastname: Dong
authors.affiliation: National Institute of Biological Sciences, Beijing, China; Graduate School of Peking Union Medical College, Beijing, China.
authors.forename: Li-Lin
authors.initials: LL
authors.lastname: Du
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D004264:DNA Topoisomerases, Type I / Q000235:genetics / Q000378:metabolism; D004271:DNA, Fungal / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D045585:Flap Endonucleases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D011485:Protein Binding; D012568:Schizosaccharomyces / Q000201:enzymology / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C468288:Cdc24 protein, S pombe; D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; C085979:RAD16 protein, S pombe; C079010:SWI10 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; C493531:Dna2 protein, S pombe; D045585:Flap Endonucleases; D004265:DNA Helicases; C106462:Rqh1 protein, S pombe; D004264:DNA Topoisomerases, Type I