Cell division cycle 7-related protein kinase

Cell division cycle 7 homolog (S. cerevisiae)
Identifiers
Symbols	CDC7; CDC7L1; HsCDC7; Hsk1; MGC117361; MGC126237; MGC126238; huCDC7
External IDs	OMIM: 603311 MGI: 1309511 HomoloGene: 31166 GeneCards: CDC7 Gene
EC number	2.7.11.1
Gene Ontology Molecular function • nucleotide binding • protein serine/threonine kinase activity • protein binding • ATP binding • kinase activity • metal ion binding Cellular component • nucleus • nucleoplasm • nucleoplasm • cytoplasm Biological process • cell cycle checkpoint • G1/S transition of mitotic cell cycle • M/G1 transition of mitotic cell cycle • mitotic cell cycle • DNA replication • positive regulation of cell proliferation • phosphorylation • regulation of S phase • cell division Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8317	12545
Ensembl	ENSG00000097046	ENSMUSG00000029283
UniProt	O00311	Q9CSF4
RefSeq (mRNA)	NM_001134419.1	NM_009863.2
RefSeq (protein)	NP_001127891.1	NP_033993.2
Location (UCSC)	Chr 1: 91.97 – 91.99 Mb	Chr 5: 107.39 – 107.41 Mb
PubMed search	[1]	[2]

Cell division cycle 7-related protein kinase is an enzyme that in humans is encoded by the CDC7 gene.^[1][2][3]

The product encoded by this gene is predominantly localized in the nucleus and is a cell division cycle protein with kinase activity. Although expression levels of the protein appear to be constant throughout the cell cycle, the protein kinase activity appears to increase during S phase. It has been suggested that the protein is essential for initiation of DNA replication and that it plays a role in regulating cell cycle progression. Overexpression of this gene product may be associated with neoplastic transformation for some tumors. Additional transcript sizes have been detected, suggesting the presence of alternative splicing.^[3]

Contents 1 General Information About CDC7 2 Cell Cycle Regulation 3 Cdc7 and Replication 4 Interactions 5 References 6 Further reading

General Information About CDC7

Cell division cycle 7 (CDC7) is a gene that codes for the protein Cdc7 kinase . The Cdc7 kinase is involved in regulation of the cell cycle at the point of chromosmal DNA replication.^[4] The cell cycle consists of four different phases including G1, S, G2, and M phase; different functions are able to occur at each phase of the cell’s life. Replication of DNA occurs in the S phase of the cycle. The gene CDC7 appears to be conserved throughout eukaryotic evolution; this means that most eukaryotic cells have the Cdc7 kinase protein. Eukaryotes are cells that have membrane bound compartments that look like “little organs” called organelles; plants, insects, mammls, and yeasts are all examples of eukaryotes. The protein is a serine-threonine kinase that is activated by another protein called either Dbf4 in the yeast Saccharomyces cerevisiae or ASK in mammals. The Cdc7/Dbf4 complex adds a phosphate group to the minichromosome maintenance (MCM) protein complex allowing for the initiation of DNA replication in mitosis (as explained in the Cdc7 and Replication section below). Mitosis is a process of replication where the daughter cells are exact copies, or clones, of the original mother cell.

Cell Cycle Regulation

The gene, CDC7, is involved in the regulation of cell cycle because of the gene product Cdc7 kinase. The protein is expressed at constant levels throughout the cell cycle. The gene coding for the Dbf4 or ASK protein is regulated during the different phases of cell cycle. The concentration of Dbf4 at the G1/S transition of the cell cycle is higher than the concentration at the M/G1 transition. This tells us that there is Dbf4 expressed around the time for replication,right after replication is over the protein levels drop. Because the two proteins, Cdc7 and Dbf4, must form a complex before activating the MCM complex the regulation of one protein is sufficient for both.

It has been shown that CDC7 is important for replication. There are a number of ways the protein expression has been altered leading to problems. In mouse embryonic stem cells (ESCs) Cdc7 is needed for proliferation. Without the CDC7 gene DNA synthesis is stopped, and the ESCs do not grow. With the loss of function of Cdc7 in ESCs the S phase is stopped at the G2/M checkpoint. Recombinational repair (RR) is done at this point to try to fix the CDC7 gene so replication can occur. By copying and replacing the altered area with a very similar area on the sister homolog chromosome, the gene can be replicated as if nothing was ever wrong on the chromosome. However, when the cell enters this arrested state, levels of p53 may increase. These increased levels of p53 may initiate cell death.^[4]

Cdc7 and Replication

After chromatin undergoes changes in telophase of mitosis, the hexameric protein complex of Mcm proteins 2-7 forms part of the prereplicative complex (preRC) by binding to the chromatin and other aiding proteins (Cdc6 and Cdt1).^[5] Mitosis occurs during M phase of the cell cycle and has a number of stages; telophase is the end stage of mitosis when the replication of chromosomes is complete, but separation has not occurred.

The Cdc7/Dbf4 kinase complex, along with another serine-threonine kinase, Cyclin-dependent kinase (Cdk), phosphorylates the preRC which activates it at the G1/S transition. The Dbf4 tethers itself to part of the preRC, the origin recognition complex (ORC). Since Cdc7 is attached to the Dbf4 protein the entire complex is held in place during replication. This activation of MCM 2 leads to helicase activity of the MCM complex at the origin of replication. This is most likely due to the change in conformation allowing the remainder of replication machinery proteins to be loaded. DNA replication can begin after all the necessary proteins are in place.^[6]

Interactions

Cell division cycle 7-related protein kinase has been shown to interact with MCM5,^[7] ORC1L,^[7] MCM7,^[7] DBF4,^[7][8][9] MCM2,^[7] MCM4^[7] and ORC6L.^[7]

References

Further reading