Knockdown of human MCM10 activates G2 checkpoint pathway.
MCM10 has been shown to be a component for the elongation step of chromosome replication in model organisms such as yeast. In the accompanying manuscript [J.H. Park, S.W. Bang, Y. Jeon, S. Kang, D.S. Hwang, Knockdown of human MCM10 exhibits delayed and incomplete chromosome replication, Biochem. Biophys. Res. Commun. (2007) 365 (2008) 575-582.], we reported that knockdown of human MCM10 protein exhibits delayed and incomplete chromosomal DNA replication. In this report, we examined the consequences of the delayed and incomplete chromosome replication in the cell cycle. Defective and incomplete chromosome replication by MCM10 knockdown activated a checkpoint pathway, composed of Chk1 and Cdc25, that inhibited Cdk1. Chk2 appeared not to be involved in the Cdk1 inhibition. The function of Cdk1 is necessary for the transition from G2 to mitotic phase, thereby Cdk1 inhibition by checkpoint arrested MCM10-knockdown cells in G2 phase. The prolonged depletion of MCM10 resulted in DNA damage followed by cell death. These results indicate that MCM10 protein is essential for maintaining genome integrity as well as cell cycle progression.
Park
Jong Hoon
JH
Department of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Bang
Sung Woong
SW
Kim
Sung Ho
SH
Hwang
Deog Su
DS
D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D002877:Chromosomes, Human / Q000235:genetics; D053960:DNA Breaks; D004261:DNA Replication / Q000235:genetics; D016195:G2 Phase / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D064110:Minichromosome Maintenance Proteins; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D020687:cdc25 Phosphatases / Q000378:metabolism
D018797:Cell Cycle Proteins; C489613:MCM10 protein, human; D034741:RNA, Small Interfering; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C000605867:CHEK1 protein, human; C578634:CHEK2 protein, human; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases; D020687:cdc25 Phosphatases; D064110:Minichromosome Maintenance Proteins