Vertebrate cells genetically deficient for Cdc14A or Cdc14B retain DNA damage checkpoint proficiency but are impaired in DNA repair.
A recent study suggested that human Cdc14B phosphatase has a central function in the G2 DNA damage checkpoint. In this study, we show that chicken DT40, human HCT116, and human telomerase reverse transcription-immortalized retinal pigment epithelial cells deleted for the Cdc14A or Cdc14B gene are DNA damage checkpoint proficient and arrest efficiently in G2 in response to irradiation. Cdc14A knockout (KO) or Cdc14B-KO cells also maintain normal levels of Chk1 and Chk2 activation after irradiation. Surprisingly, however, irradiation-induced gamma-H2A.X foci and DNA double-strand breaks persist longer in Cdc14A-KO or Cdc14B-KO cells than controls, suggesting that Cdc14 phosphatases are required for efficient DNA repair.
Mocciaro
Annamaria
A
Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Allianz, 69117 Heidelberg, Germany.
Berdougo
Eli
E
Zeng
Kang
K
Black
Elizabeth
E
Vagnarelli
Paola
P
Earnshaw
William
W
Gillespie
David
D
Jallepalli
Prasad
P
Schiebel
Elmar
E
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D002645:Chickens; D004249:DNA Damage; D004260:DNA Repair; D054637:Dual-Specificity Phosphatases / Q000235:genetics / Q000502:physiology*; D045325:HCT116 Cells; D006801:Humans; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000502:physiology*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases
D018797:Cell Cycle Proteins; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C000605867:CHEK1 protein, human; C578634:CHEK2 protein, human; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases; D010744:Phosphoric Monoester Hydrolases; C120902:CDC14A protein, human; C474200:CDC14B protein, human; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases