A second human Dbf4/ASK-related protein, Drf1/ASKL1, is required for efficient progression of S and M phases
| Autor: | Etsuko Matsui, Ai Ishii, Hisao Masai, Chika Taniyama, Ken-ichi Arai, Naoko Yoshizawa-Sugata |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
DNA Replication
G2 Phase Time Factors Transcription Genetic Amino Acid Motifs Detergents Formins Mitosis Eukaryotic DNA replication Cell Cycle Proteins Biology Protein Serine-Threonine Kinases Transfection Biochemistry S Phase Humans Nuclear protein Phosphorylation RNA Small Interfering Luciferases Molecular Biology S phase Adaptor Proteins Signal Transducing Cell Proliferation Glutathione Transferase Cell Nucleus Cell growth Nocodazole Cell Cycle DNA replication Nuclear Proteins Minichromosome Maintenance Complex Component 2 Cell Biology DNA Cell cycle Molecular biology Cell biology Bromodeoxyuridine Origin recognition complex Cell Division DNA Damage HeLa Cells Protein Binding Subcellular Fractions Thymidine |
| Zdroj: | The Journal of biological chemistry. 280(13) |
| ISSN: | 0021-9258 |
| Popis: | Cdc7-Dbf4 kinase is conserved through evolution and regulates initiation and progression of DNA replication. In human, ASK/hsDbf4 binds and activates huCdc7 during S phase and this kinase complex is essential for DNA replication and cell proliferation. Drf1/ASKL1, a second human Dbf4/ASK-related protein, shares three conserved Dbf4 motifs previously identified on all of the Dbf4-related molecules. Drf1/ASKL1 can bind and activate huCdc7, and Cdc7-ASKL1 complex phosphorylates MCM2. ASKL1 transcription and protein levels oscillate during cell cycle and increase at late S to G2/M phases. The protein is detected predominantly in the nuclear-soluble fraction but not in the chromatin-bound fraction. Inhibition of Drf1/ASKL1 expression by siRNA results in attenuation of cell growth and in the increase of late S and G2/M phase population. siRNA treatment on synchronized cell population revealed that S phase progression is delayed when ASKL1 protein level is decreased. S phase delay may be linked to replication fork block, because increased levels of gammaH2AX and activated form of Chk2 are detected with ASKL1 siRNA in the absence of any additional DNA damages. Furthermore, mitotic progression is retarded in ASKL1 or Cdc7 siRNA-treated cells. Our results suggest that ASKL1 in a complex with Cdc7 may play a role in normal progression of both S and M phases. |
| Databáze: | OpenAIRE |
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