Levels of MCM4 phosphorylation and DNA synthesis in DNA replication block checkpoint control.
Blockage of a DNA replication fork movement not only stabilizes the fork structure but also prevents initiation of DNA replication. We reported that MCM4, a subunit of a putative replicative DNA helicase, is extensively phosphorylated in the presence of hydroxyurea (HU) or after exposure to UV irradiation. Here we examined the relationship between levels of MCM4 phosphorylation and DNA synthesis during DNA replication checkpoint control and after release of the control. The results suggest that there is roughly inverse correlation between these two levels; namely the higher the level of MCM4 phosphorylation, the lower the level of DNA synthesis. The presence of HU or UV irradiation can stimulate phosphorylation at several cyclin-dependent kinase (CDK) sites in MCM4, which can lead to inhibition of MCM4/6/7 helicase activity. These results are consistent with the notion that the phosphorylation of MCM4 is involved in regulation of DNA synthesis in the checkpoint control.
Ishimi
Yukio
Y
Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan. yukio@libra.ls.m-kagaku.co.jp
Komamura-Kohno
Yuki
Y
Karasawa-Shimizu
Kumiko
K
Yamada
Kouichi
K
D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000378:metabolism* / Q000502:physiology* / Q000528:radiation effects; D018844:Cyclin-Dependent Kinases; D004265:DNA Helicases; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology* / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D064148:Minichromosome Maintenance Complex Component 4; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000032:analysis / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D018844:Cyclin-Dependent Kinases; D004265:DNA Helicases; C099243:MCM4 protein, human; D064148:Minichromosome Maintenance Complex Component 4; D006918:Hydroxyurea