Per3, a circadian gene, is required for Chk2 activation in human cells.
PER3 is a member of the PERIOD genes, but does not play essential roles in the circadian clock. Depletion of Per3 by siRNA almost completely abolished activation of checkpoint kinase 2 (Chk2) after inducing DNA damage in human cells. In addition, Per3 physically interacted with ATM and Chk2. Per3 overexpression induced Chk2 activation in the absence of exogenous DNA damage, and this activation depended on ATM. Per3 overexpression also led to the inhibition of cell proliferation and apoptotic cell death. These combined results suggest that Per3 is a checkpoint protein that plays important roles in checkpoint activation, cell proliferation and apoptosis.
Department of Biology Education, Seoul National University, Seoul, Republic of Korea.
Jun-Sub
JS
Im
Bo-Hyeon
BH
Jung
Sang-Eun
SE
Kim
Kun-Ho
KH
Lee
Joon-Kyu
JK
Lee
D017209:Apoptosis / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation; D064447:Checkpoint Kinase 2; D057906:Circadian Clocks / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D004789:Enzyme Activation / Q000235:genetics; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D056950:Period Circadian Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C512644:PER3 protein, human; D056950:Period Circadian Proteins; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D064447:Checkpoint Kinase 2; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases