Cdc14A and Cdc14B Redundantly Regulate DNA Double-Strand Break Repair.
Cdc14 is a phosphatase that controls mitotic exit and cytokinesis in budding yeast. In mammals, the two Cdc14 homologues, Cdc14A and Cdc14B, have been proposed to regulate DNA damage repair, whereas the mitotic exit and cytokinesis rely on another phosphatase, PP2A-B55α. It is unclear if the two Cdc14s work redundantly in DNA repair and which repair pathways they participate in. More importantly, their target(s) in DNA repair remains elusive. Here we report that Cdc14B knockout (Cdc14B(-/-)) mouse embryonic fibroblasts (MEFs) showed defects in repairing ionizing radiation (IR)-induced DNA double-strand breaks (DSBs), which occurred only at late passages when Cdc14A levels were low. This repair defect could occur at early passages if Cdc14A levels were also compromised. These results indicate redundancy between Cdc14B and Cdc14A in DSB repair. Further, we found that Cdc14B deficiency impaired both homologous recombination (HR) and nonhomologous end joining (NHEJ), the two major DSB repair pathways. We also provide evidence that Cdh1 is a downstream target of Cdc14B in DSB repair.
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA.
Han
H
Lin
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA.
Kyungsoo
K
Ha
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA.
Guojun
G
Lu
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA.
Xiao
X
Fang
Beijing Proteome Research Center, Beijing, China.
Ranran
R
Cheng
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA.
Qiuhong
Q
Zuo
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA Beijing Proteome Research Center, Beijing, China pzhang@bcm.edu.
Pumin
P
Zhang
D000818:Animals; D064200:Cdh1 Proteins / Q000378:metabolism; D002453:Cell Cycle; D002460:Cell Line; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D059766:DNA End-Joining Repair; D004260:DNA Repair; D054637:Dual-Specificity Phosphatases / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D017353:Gene Deletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*
D064200:Cdh1 Proteins; C577585:Fzr1 protein, mouse; C541113:CDC14A protein, mouse; C541950:CDC14B protein, mouse; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases