Cell division cycle 7-related protein kinase
Encyclopedia
Cell division cycle 7-related protein kinase is an enzyme
that in humans is encoded by the CDC7 gene
.
. The Cdc7 kinase is involved in regulation of the cell cycle
at the point of chromosmal
DNA replication
. 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.
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.
and Cdt1). 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.
with MCM5
, ORC1L, MCM7
, DBF4
, MCM2
, MCM4
and ORC6L
.
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that in humans is encoded by the CDC7 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
General Information About CDC7
Cell division cycle 7 (CDC7) is a gene that codes for the protein Cdc7 kinaseKinase
In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...
. The Cdc7 kinase is involved in regulation of the cell cycle
Cell cycle
The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...
at the point of chromosmal
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
DNA replication
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...
. 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
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
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
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...
(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
Cell growth
The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...
. 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.
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 (Cdc6Cdc6
Cdc6, or Cell Division Cycle 6, is a protein in eukaryotic cells that is studied in the budding yeast Saccharomyces cerevisiae. It is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle that coordinate...
and Cdt1). 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
Helicase
Helicases are a class of enzymes vital to all living organisms. They are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separating two annealed nucleic acid strands using energy derived from ATP hydrolysis.-Function:Many cellular processes Helicases are a...
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.
Interactions
Cell division cycle 7-related protein kinase has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with MCM5
MCM5
DNA replication licensing factor MCM5 is a protein that in humans is encoded by the MCM5 gene.-Interactions:MCM5 has been shown to interact with ORC2L, MCM7, STAT1, MCM2, Cell division cycle 7-related protein kinase, MCM3 and ORC6L.-Further reading:...
, ORC1L, MCM7
MCM7
DNA replication licensing factor MCM7 is a protein that in humans is encoded by the MCM7 gene.-Interactions:MCM7 has been shown to interact with Replication protein A1, ORC3L, Retinoblastoma protein, MCM5, MCM6, ORC1L, ORC2L, ORC5L, MCM4, MCM3, CDC6, MNAT1, DBF4, MCM2, UBE3A, CDC45-related protein...
, DBF4
DBF4
Protein DBF4 homolog A is a protein that in humans is encoded by the DBF4 gene.-Interactions:DBF4 has been shown to interact with ORC2L, MCM7, Cell division cycle 7-related protein kinase, MCM3 and ORC6L.-Further reading:...
, MCM2
MCM2
DNA replication licensing factor MCM2 is a protein that in humans is encoded by the MCM2 gene.-Interactions:MCM2 has been shown to interact with Replication protein A1, AKAP8, MCM5, MCM6, MCM7, ORC1L, ORC2L, ORC4L, ORC5L, MCM4, MCM3 and Cell division cycle 7-related protein kinase.-Further reading:...
, MCM4
MCM4
DNA replication licensing factor MCM4 is a protein that in humans is encoded by the MCM4 gene.-Interactions:MCM4 has been shown to interact with ORC1L, ORC2L, Replication protein A1, ORC4L, ORC5L, ORC3L, MCM6, MCM7, MCM2, Cell division cycle 7-related protein kinase and ORC6L.-Further reading:...
and ORC6L
ORC6L
Origin recognition complex subunit 6 is a protein that in humans is encoded by the ORC6L gene.-Background:The origin recognition complex is a highly conserved six subunit protein complex essential for the initiation of the DNA replication in eukaryotic cells...
.