Nek6 is involved in G2/M phase cell cycle arrest through DNA damage-induced phosphorylation.
Nek6 is a recently identified NIMA-related kinase that is required for mitotic cell cycle progression. In the present study, we examined the role of Nek6 in the DNA damage response. We found that Nek6 is phosphorylated upon IR and UV irradiation through the DNA damage checkpoint in vivo. Nek6 is also directly phosphorylated by the checkpoint kinases Chk1 and Chk2 in vitro. Notably, Nek6 activation during mitosis is completely abolished by IR and UV irradiation. Moreover, the ectopic expression of Nek6 overrides DNA damage-induced G(2)/M arrest. These results suggest that Nek6 is a novel target of the DNA damage checkpoint and that the inhibition of Nek6 activity is required for proper cell cycle arrest in the G(2)/M phase upon DNA damage.
Lee
Min-Young
MY
Department of Biochemistry, College of Medicine, Dong-A University, South Korea.
Kim
Hyun-Ju
HJ
Kim
Myoung-Ae
MA
Jee
Hye Jin
HJ
Kim
Ae Jeong
AJ
Bae
Yoe-Sik
YS
Park
Joo-In
JI
Chung
Jay H
JH
Yun
Jeanho
J
D002455:Cell Division; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D004789:Enzyme Activation; D016195:G2 Phase; D006367:HeLa Cells; D006801:Humans; D000072379:NIMA-Related Kinases; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C000605867:CHEK1 protein, human; C578634:CHEK2 protein, human; D000071877:Checkpoint Kinase 1; D000072379:NIMA-Related Kinases; C442331:NIMA-related kinase 6; D017346:Protein Serine-Threonine Kinases