Essential role of Chk1 in S phase progression through regulation of RNR2 expression.
Chk1 is an essential kinase for maintaining genome integrity and cell cycle checkpoints through phosphorylating several downstream targets. Recently, we demonstrated that Chk1 is also required for cell proliferation in somatic cells under unperturbed condition through regulating transcription of several genes. Here, we show that Chk1 is required for S phase progression and RNR2 is a critical downstream target of genes transcriptionally regulated by Chk1. Hence, although RNR2 expression reached maximum at S phase in the presence of Chk1, Chk1 depletion arrested the cell cycle at S phase and reduced RNR2 expression at both mRNA and protein levels. Ectopic expression of RNR2 failed to rescue the S phase arrest observed in Chk1 depleted cells, suggesting the presence of an additional Chk1-target(s) for completion of S phase other than RNR2. Therefore, our results suggest that Chk1 is required for DNA replication at least through regulating RNR2 gene transcription.
Naruyama
Hiromichi
H
Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Shimada
Midori
M
Niida
Hiroyuki
H
Zineldeen
Doaa H
DH
Hashimoto
Yoshihiro
Y
Kohri
Kenjiro
K
Nakanishi
Makoto
M
D000818:Animals; D002460:Cell Line; D000071877:Checkpoint Kinase 1; D004261:DNA Replication; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D012262:Ribonucleoside Diphosphate Reductase; D012264:Ribonucleotide Reductases / Q000235:genetics*; D016196:S Phase / Q000235:genetics*; D014158:Transcription, Genetic
D012264:Ribonucleotide Reductases; C108427:ribonucleotide reductase R2 subunit; D012262:Ribonucleoside Diphosphate Reductase; C498690:Rrm1 protein, mouse; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1; C000605869:Chek1 protein, mouse