What has the cloning of the ATM gene told us about ataxia telangiectasia?
- PMID: 9587073
- DOI: 10.1080/095530098142185
What has the cloning of the ATM gene told us about ataxia telangiectasia?
Abstract
Purpose: To review what the cloning of the ATM gene has told us about ataxia telangiectasia (A-T).
Conclusions: Perhaps the most interesting and potentially useful finding following the cloning of the gene has been the discovery of homologies with various previously known PIK related kinases. There is also a very wide range of mutations associated with A-T and it is clear that some ATM mutations can lessen the severity of both the clinical and cellular features of the disorder. The function(s) of ATM remain an enigma. There are several indications of its involvement in protecting the cell from the effects of ionizing radiation and radiomimetic agents, although the pathways that involve p53 and c-Abl are far from clear. Expression of AIM in tissue culture cells can reverse the cellular features of A-T, particularly the increased level of radiosensitivity. The localization of ATM on meiotic chromosomes and its speculated role in meiotic recombination is an important finding. Finally, cloning the ATM gene has allowed the development of mouse models, which are providing information about A-T and will be crucial for testing future treatments for the disorder.
Similar articles
-
ATM: the protein encoded by the gene mutated in the radiosensitive syndrome ataxia-telangiectasia.Int J Radiat Biol. 1999 Oct;75(10):1201-14. doi: 10.1080/095530099139359. Int J Radiat Biol. 1999. PMID: 10549596 Review.
-
Radiosensitivity and oxidative signalling in ataxia telangiectasia: an update.Radiother Oncol. 1998 May;47(2):113-23. doi: 10.1016/s0167-8140(98)00027-9. Radiother Oncol. 1998. PMID: 9683357 Review.
-
ATM: the product of the gene mutated in ataxia-telangiectasia.Int J Biochem Cell Biol. 1999 Jul;31(7):735-40. doi: 10.1016/s1357-2725(99)00028-x. Int J Biochem Cell Biol. 1999. PMID: 10467728 Review.
-
Ataxia-telangiectasia, cancer and the pathobiology of the ATM gene.Clin Genet. 1999 May;55(5):289-304. doi: 10.1034/j.1399-0004.1999.550501.x. Clin Genet. 1999. PMID: 10422797 Review.
-
Genotype-phenotype relationships in ataxia-telangiectasia and variants.Am J Hum Genet. 1998 Mar;62(3):551-61. doi: 10.1086/301755. Am J Hum Genet. 1998. PMID: 9497252 Free PMC article.
Cited by
-
Functional and computational assessment of missense variants in the ataxia-telangiectasia mutated (ATM) gene: mutations with increased cancer risk.Hum Mutat. 2009 Jan;30(1):12-21. doi: 10.1002/humu.20805. Hum Mutat. 2009. PMID: 18634022 Free PMC article.
-
STAT1 is overexpressed in tumors selected for radioresistance and confers protection from radiation in transduced sensitive cells.Proc Natl Acad Sci U S A. 2004 Feb 10;101(6):1714-9. doi: 10.1073/pnas.0308102100. Epub 2004 Jan 30. Proc Natl Acad Sci U S A. 2004. PMID: 14755057 Free PMC article.
-
Effects of the protein kinase inhibitors wortmannin and KN62 on cellular radiosensitivity and radiation-activated S phase and G1/S checkpoints in normal human fibroblasts.Br J Cancer. 1999 Nov;81(6):959-65. doi: 10.1038/sj.bjc.6690793. Br J Cancer. 1999. PMID: 10576651 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Molecular Biology Databases
Research Materials
Miscellaneous
