Fission Yeast Pxd1 Promotes Proper DNA Repair by Activating Rad16XPF and Inhibiting Dna2

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. © 2014 zhang et al.