Publication Date:
2000-01-05
Description:
The hCHK2 gene encodes the human homolog of the yeast Cds1 and Rad53 G2 checkpoint kinases, whose activation in response to DNA damage prevents cellular entry into mitosis. Here, it is shown that heterozygous germ line mutations in hCHK2 occur in Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in the TP53 gene. These observations suggest that hCHK2 is a tumor suppressor gene conferring predisposition to sarcoma, breast cancer, and brain tumors, and they also provide a link between the central role of p53 inactivation in human cancer and the well-defined G2 checkpoint in yeast.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bell, D W -- Varley, J M -- Szydlo, T E -- Kang, D H -- Wahrer, D C -- Shannon, K E -- Lubratovich, M -- Verselis, S J -- Isselbacher, K J -- Fraumeni, J F -- Birch, J M -- Li, F P -- Garber, J E -- Haber, D A -- New York, N.Y. -- Science. 1999 Dec 24;286(5449):2528-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts General Hospital Center for Cancer Risk Analysis and Harvard Medical School, Building 149, Charlestown, MA 02129, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10617473" target="_blank"〉PubMed〈/a〉
Keywords:
Alleles
;
Apoptosis
;
Brain Neoplasms/genetics
;
Breast Neoplasms/genetics
;
Checkpoint Kinase 2
;
Female
;
G1 Phase
;
*G2 Phase
;
*Genes, Tumor Suppressor
;
Genes, p53
;
Genetic Predisposition to Disease
;
*Germ-Line Mutation
;
Heterozygote
;
Humans
;
Li-Fraumeni Syndrome/enzymology/*genetics/pathology
;
Male
;
Pedigree
;
Polymorphism, Genetic
;
Protein Kinases/genetics
;
Protein-Serine-Threonine Kinases/*genetics/metabolism
;
Sarcoma/genetics
;
Signal Transduction
;
Tumor Cells, Cultured
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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