CHEK2
Encyclopedia
CHEK2 is the official symbol for the human gene
CHK2 checkpoint homolog. It is located on the long (q) arm of chromosome 22.
encoded by this gene, CHK2 a protein kinase
that is activated in response to DNA damage and is involved in cell cycle arrest
.
In response to DNA damage and replication blocks, cell cycle progression is halted through the control of cell cycle regulators. The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. It contains a forkhead-associated protein interaction domain
essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. When activated, the encoded protein is known to inhibit CDC25C phosphatase
, preventing entry into mitosis
, and has been shown to stabilize the tumor suppressor protein p53
, leading to cell cycle arrest in G1. In addition, this protein interacts with and phosphorylates BRCA1
, allowing BRCA1 to restore survival after DNA damage.
when it ought to have done so. Thus, a mutation leads to an increased susceptibility to cancer. The following conditions are examples of such cancers.
-mutation at position 1100 of the CHEK2 gene is associated with an increased risk of breast cancer, particularly in the European population. In women of Northern and Eastern European descent CHEK2*1100delC carrier status confers a 2-3 fold risk of breast cancer. In this ethnic group, women with a familial history of breast cancer have a 4.8 fold risk of breast cancer equal to a lifetime risk of breast cancer of 37%.
, however the relative high prevalence of the mutation in the general population (0.5%) has made this association unlikely.
with PLK1
, MDC1
, MSH2
, GINS2
, PLK3
, MUS81
and BRCA1
.
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...
CHK2 checkpoint homolog. It is located on the long (q) arm of chromosome 22.
Function
The proteinProtein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
encoded by this gene, CHK2 a protein kinase
Protein kinase
A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins...
that is activated in response to DNA damage and is involved in cell cycle arrest
Cell cycle checkpoint
Cell cycle checkpoints are control mechanisms that ensure the fidelity of cell division in eukaryotic cells. These checkpoints verify whether the processes at each phase of the cell cycle have been accurately completed before progression into the next phase...
.
In response to DNA damage and replication blocks, cell cycle progression is halted through the control of cell cycle regulators. The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. It contains a forkhead-associated protein interaction domain
Forkhead-associated domain
In molecular biology, the forkhead-associated domain is a phosphopeptide recognition domain found in many regulatory proteins. It displays specificity for phosphothreonine-containing epitopes but will also recognise phosphotyrosine with relatively high affinity...
essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. When activated, the encoded protein is known to inhibit CDC25C phosphatase
CDC25C
M-phase inducer phosphatase 3 is an enzyme that in humans is encoded by the CDC25C gene.-Interactions:CDC25C has been shown to interact with MAPK14, CHEK1, PCNA, PIN1, PLK3 and NEDD4.-Further reading:...
, preventing entry into 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...
, and has been shown to stabilize the tumor suppressor protein p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
, leading to cell cycle arrest in G1. In addition, this protein interacts with and phosphorylates BRCA1
BRCA1
BRCA1 is a human caretaker gene that produces a protein called breast cancer type 1 susceptibility protein, responsible for repairing DNA. The first evidence for the existence of the gene was provided by the King laboratory at UC Berkeley in 1990...
, allowing BRCA1 to restore survival after DNA damage.
Related conditions
A mutation in CHEK2 gene results in decreased DNA-repair, or inability of the cell to undergo apoptosisApoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
when it ought to have done so. Thus, a mutation leads to an increased susceptibility to cancer. The following conditions are examples of such cancers.
Breast cancer
A deletionDeletion
Deletion is the act of deleting or removal by striking out material, such as a word or passage, that has been removed from a body of written or printed matter.Deletion may refer to:*File deletion, a way of removing a file from a computer's file system...
-mutation at position 1100 of the CHEK2 gene is associated with an increased risk of breast cancer, particularly in the European population. In women of Northern and Eastern European descent CHEK2*1100delC carrier status confers a 2-3 fold risk of breast cancer. In this ethnic group, women with a familial history of breast cancer have a 4.8 fold risk of breast cancer equal to a lifetime risk of breast cancer of 37%.
Li-Fraumeni syndrome
The CHEK2*1100delC mutation was originally associated with the Li-Fraumeni syndromeLi-Fraumeni syndrome
Li-Fraumeni syndrome is an extremely rare autosomal dominant hereditary disorder. It is named after Frederick Pei Li and Joseph F. Fraumeni, Jr., the American physicians who first recognized and described the syndrome. Li-Fraumeni syndrome greatly increases susceptibility to cancer...
, however the relative high prevalence of the mutation in the general population (0.5%) has made this association unlikely.
Interactions
CHEK2 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 PLK1
PLK1
Serine/threonine-protein kinase PLK1, also known as polo-like kinase 1 or serine/threonine-protein kinase 13 , is an enzyme that in humans is encoded by the PLK1 gene.- Structure :...
, MDC1
MDC1
Mediator of DNA damage checkpoint protein 1 is a protein that in humans is encoded by the MDC1 gene.-Interactions:MDC1 has been shown to interact with MRE11A, H2AFX and CHEK2.-Further reading:...
, MSH2
MSH2
MSH2 is a gene commonly associated with Hereditary nonpolyposis colorectal cancer.-Interactions:MSH2 has been shown to interact with Exonuclease 1, MSH3, MSH6, CHEK2, MAX, Ataxia telangiectasia and Rad3 related and BRCA1.-Further reading:...
, GINS2
GINS2
DNA replication complex GINS protein PSF2 is a protein that in humans is encoded by the GINS2 gene.-Further reading:...
, PLK3
PLK3
Polo-like kinase 3 , also known as PLK3, is an enzyme which in humans is encoded by the PLK3 gene.- Function :Cytokine-inducible kinase is a putative serine/threonine kinase. CNK contains both a catalytic domain and a putative regulatory domain...
, MUS81
MUS81
Crossover junction endonuclease MUS81 is an enzyme that in humans is encoded by the MUS81 gene.-Further reading:...
and BRCA1
BRCA1
BRCA1 is a human caretaker gene that produces a protein called breast cancer type 1 susceptibility protein, responsible for repairing DNA. The first evidence for the existence of the gene was provided by the King laboratory at UC Berkeley in 1990...
.