| CHK2 checkpoint homolog (S. pombe)
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| PDB rendering based on 1gxc.
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| Available structures: 1gxc, 2cn5, 2cn8
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| Identifiers
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| Symbol(s)
| CHEK2; CDS1; CHK2; HuCds1; LFS2; PP1425; RAD53
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| External IDs
| OMIM: 604373 MGI: 1355321 Homologene: 38289
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| Gene Ontology
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| Molecular Function:
| • nucleotide binding
• magnesium ion binding
• protein serine/threonine kinase activity
• protein binding
• ATP binding
• transferase activity
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| Cellular Component:
| • nucleus
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| Biological Process:
| • DNA damage checkpoint
• protein amino acid phosphorylation
• response to DNA damage stimulus
• cell cycle
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| RNA expression pattern
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More reference expression data
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| Orthologs
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| Human
| Mouse
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| Entrez
| 11200
| 50883
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| Ensembl
| ENSG00000183765
| ENSMUSG00000029521
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| Uniprot
| O96017
| Q543W6
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| Refseq
| NM_001005735 (mRNA)
NP_001005735 (protein)
| NM_016681 (mRNA)
NP_057890 (protein)
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| Location
| Chr 22: 27.41 - 27.47 Mb
| Chr 5: 111.08 - 111.11 Mb
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| Pubmed search
| [1]
| [2]
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CHEK2 is the official symbol for the human gene CHK2 checkpoint homolog. It is located on the long (q) arm of chromosome 22.
Additional recommended knowledge
Function
The protein coded by this gene is CHK2. This protein prevents the cell from dividing or growing too fast. Thus, the gene is a tumor suppressor gene, because prevents tumors from becoming malignant.
DNA can be damaged by e.g.:
- UV-light from the sun
- other kinds of radiation
- toxic chemicals
- exchange of genetic material between chromosomes
CHEK2 responds to genetic damage by producing its protein CHK2, which in turn interacts with other proteins, for example p53.
As a result, the cell either stops the cell cycle and therefore its proliferation until the damage is repaired, or it self-destructs (apoptosis). Otherwise, the damage or mutation could make the cell a cancer-cell, developing a tumor.
Related conditions
A mutation in CHEK2 gene results in decreased DNA-repair, or inability of the cell to undergo apoptosis 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 deletion-mutation at position 1100 of the CHEK2 gene is associated with an increased risk of breast cancer, particularly in the European population. The mutation changes the form of the CHK2 protein, making it short and nonfunctional.[1]
Li-Fraumeni syndrome
Most cases of Li-Fraumeni syndrome is caused by a mutation in the TP53 gene. However, this condition has also been identified as a result of CHEK2-mutations in several families.[1]
References
- ^ a b http://ghr.nlm.nih.gov/gene=chek2/
Further reading
- Caspari T (2000). "How to activate p53.". Curr. Biol. 10 (8): R315-7. PMID 10801407.
- McGowan CH (2002). "Checking in on Cds1 (Chk2): A checkpoint kinase and tumor suppressor.". Bioessays 24 (6): 502-11. doi:10.1002/bies.10101. PMID 12111733.
- Honrado E, Osorio A, Palacios J, Benitez J (2006). "Pathology and gene expression of hereditary breast tumors associated with BRCA1, BRCA2 and CHEK2 gene mutations.". Oncogene 25 (43): 5837-45. doi:10.1038/sj.onc.1209875. PMID 16998498.
- Nevanlinna H, Bartek J (2006). "The CHEK2 gene and inherited breast cancer susceptibility.". Oncogene 25 (43): 5912-9. doi:10.1038/sj.onc.1209877. PMID 16998506.
- Peng CY, Graves PR, Thoma RS, et al. (1997). "Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216.". Science 277 (5331): 1501-5. PMID 9278512.
- Lykidis A, Jackson PD, Rock CO, Jackowski S (1998). "The role of CDP-diacylglycerol synthetase and phosphatidylinositol synthase activity levels in the regulation of cellular phosphatidylinositol content.". J. Biol. Chem. 272 (52): 33402-9. PMID 9407135.
- Lindsay HD, Griffiths DJ, Edwards RJ, et al. (1998). "S-phase-specific activation of Cds1 kinase defines a subpathway of the checkpoint response in Schizosaccharomyces pombe.". Genes Dev. 12 (3): 382-95. PMID 9450932.
- Matsuoka S, Huang M, Elledge SJ (1998). "Linkage of ATM to cell cycle regulation by the Chk2 protein kinase.". Science 282 (5395): 1893-7. PMID 9836640.
- Martinho RG, Lindsay HD, Flaggs G, et al. (1999). "Analysis of Rad3 and Chk1 protein kinases defines different checkpoint responses.". EMBO J. 17 (24): 7239-49. doi:10.1093/emboj/17.24.7239. PMID 9857181.
- Blasina A, de Weyer IV, Laus MC, et al. (1999). "A human homologue of the checkpoint kinase Cds1 directly inhibits Cdc25 phosphatase.". Curr. Biol. 9 (1): 1-10. PMID 9889122.
- Brown AL, Lee CH, Schwarz JK, et al. (1999). "A human Cds1-related kinase that functions downstream of ATM protein in the cellular response to DNA damage.". Proc. Natl. Acad. Sci. U.S.A. 96 (7): 3745-50. PMID 10097108.
- Chaturvedi P, Eng WK, Zhu Y, et al. (1999). "Mammalian Chk2 is a downstream effector of the ATM-dependent DNA damage checkpoint pathway.". Oncogene 18 (28): 4047-54. doi:10.1038/sj.onc.1202925. PMID 10435585.
- Ouyang B, Li W, Pan H, et al. (1999). "The physical association and phosphorylation of Cdc25C protein phosphatase by Prk.". Oncogene 18 (44): 6029-36. doi:10.1038/sj.onc.1202983. PMID 10557092.
- Dunham I, Shimizu N, Roe BA, et al. (1999). "The DNA sequence of human chromosome 22.". Nature 402 (6761): 489-95. doi:10.1038/990031. PMID 10591208.
- Bell DW, Varley JM, Szydlo TE, et al. (2000). "Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome.". Science 286 (5449): 2528-31. PMID 10617473.
- Chehab NH, Malikzay A, Appel M, Halazonetis TD (2000). "Chk2/hCds1 functions as a DNA damage checkpoint in G(1) by stabilizing p53.". Genes Dev. 14 (3): 278-88. PMID 10673500.
- Hirao A, Kong YY, Matsuoka S, et al. (2000). "DNA damage-induced activation of p53 by the checkpoint kinase Chk2.". Science 287 (5459): 1824-7. PMID 10710310.
- Lee JS, Collins KM, Brown AL, et al. (2000). "hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response.". Nature 404 (6774): 201-4. doi:10.1038/35004614. PMID 10724175.
- Zhou BB, Chaturvedi P, Spring K, et al. (2000). "Caffeine abolishes the mammalian G(2)/M DNA damage checkpoint by inhibiting ataxia-telangiectasia-mutated kinase activity.". J. Biol. Chem. 275 (14): 10342-8. PMID 10744722.
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