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CDC7 kinase phosphorylates serine residues adjacent to acidic amino acids in the minichromosome maintenance 2 protein.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Cho, Woo-Chul Lee, Young-Joo Kong, Soo-Im Hurwitz, Jerard Lee, J. K. |
| Copyright Year | 2006 |
| Abstract | Cdc7 is an essential kinase required for the initiation of eukaryotic DNA replication. Previous studies in many species showed that the minichromosome maintenance complex is a major physiological target of this kinase. In this study, we have mapped the sites in human Mcm2 protein that are phosphorylated by Cdc7. The in vitro phosphorylation of several Mcm2 truncated proteins and peptides revealed that Mcm2 contains two major ((5)S and (53)S) and at least three minor phosphorylation sites ((4)S, (7)S, and (59)T) located at the N-terminal region. Alanine substitution experiments with Mcm2 peptides showed that the phosphorylation of (5)S and (53)S by Cdc7 required the presence of an acidic amino acid adjacent to a serine residue. Furthermore, although Cdc7 was unable to phosphorylate a Mcm2 peptide (spanning amino acids 19-30 and containing (26)S and (27)S), it phosphorylated (26)S efficiently when this peptide contained a chemically synthesized phospho-(27)S modification. Hence, additional Cdc7 phosphorylation sites could be generated in Mcm2 by its prior phosphorylation by a cyclin-dependent kinase. This finding may explain why the sequential action of cyclin-dependent and Cdc7 kinases is essential for the initiation of DNA replication. |
| Starting Page | 859 |
| Ending Page | 863 |
| Page Count | 5 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.pnas.org/content/103/31/11521.full.pdf |
| PubMed reference number | 16864800v1 |
| Volume Number | 103 |
| Issue Number | 31 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Alanine Amino Acids Amino Acids, Acidic CDC7 protein, human Contain (action) Cyclin-Dependent Kinases Cyclins DNA Replication Serine Transcription Initiation |
| Content Type | Text |
| Resource Type | Article |