OrganismHomo sapiens
Aging PhenotypeShortened life-span
Allele TypeRecessive
DescriptionPatients with ataxia-telangiectasia (AT) show decreased life span, with the maximum (as of 1985) of 52 years (Broder 1985).
Gene FunctionPositional cloning led to the identification of the ATM gene, representing AT complementation groups A, C, and D (Sanal et al, 1990; Savitsky et al, 1995). ATM codes for a checkpoint kinase in response to ionizing radiation, required for phosphorylation of multiple proteins, including p53 (Banin et al, 1998; Canman et al, 1998) BRCA1 (Cortez et al, 1999) and nibrin (Gatei et al, 2000).
Other PhenotypesPatients with AT show progressive cerebellar ataxia from early childhood and later develop telangiectases, other progressive neurologic degeneration, sinopulmonary infections and increased malignancy (see OMIM link).
HomologsS.c. TEL1
S.p. tel1
D.m. CG6535
M.m. ATM
Primary ReferenceBoder, E. Ataxia-telangiectasia: an overview. In: Gatti, R. A.; Swift, M. : Ataxia-telangiectasia: Genetics, Neuropathology and Immunology of a Degenerative Disease of Childhood. New York: Alan R. Liss (pub.) 1985. Pp. 1-63.
Other ReferencesBanin, S., Moyal, L., Shieh, S., Taya, Y., Anderson, C. W., Chessa, L., Smorodinsky, N. I., Prives, C., Reiss, Y., Shiloh, Y., and Ziv, Y. (1998). Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science 281, 1674-7. [Abstract]
Canman, C. E., Lim, D. S., Cimprich, K. A., Taya, Y., Tamai, K., Sakaguchi, K., Appella, E., Kastan, M. B., and Siliciano, J. D. (1998). Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science 281, 1677-9. [Abstract]
Cortez, D., Wang, Y., Qin, J., and Elledge, S. J. (1999). Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage response to double-strand breaks. Science 286, 1162-6. [Abstract]
Gatei, M., Young, D., Cerosaletti, K. M., Desai-Mehta, A., Spring, K., Kozlov, S., Lavin, M. F., Gatti, R. A., Concannon, P., and Khanna, K. (2000). ATM-dependent phosphorylation of nibrin in response to radiation exposure. Nat Genet 25, 115-9. [Abstract]
Sanal, O., Wei, S., Foroud, T., Malhotra, U., Concannon, P., Charmley, P., Salser, W., Lange, K., and Gatti, R. A. (1990). Further mapping of an ataxia-telangiectasia locus to the chromosome 11q23 region. Am J Hum Genet 47, 860-6. [Abstract]
Savitsky, K., Bar-Shira, A., Gilad, S., Rotman, G., Ziv, Y., Vanagaite, L., Tagle, D. A., Smith, S., Uziel, T., Sfez, S., and et al. (1995). A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 268, 1749-53. [Abstract]
Relevant LinksLocusLink:
KeywordsHuman, Homo sapiens, DNA damage, cancer, repair