The role of ATM in telomere structure and function

Authors
Citation
Tk. Pandita, The role of ATM in telomere structure and function, RADIAT RES, 156(5), 2001, pp. 642-647
Citations number
53
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Experimental Biology
Journal title
RADIATION RESEARCH
ISSN journal
0033-7587 → ACNP
Volume
156
Issue
5
Year of publication
2001
Part
2
Pages
642 - 647
Database
ISI
SICI code
0033-7587(200111)156:5<642:TROAIT>2.0.ZU;2-A
Abstract
Ataxia telangiectasia (AT) is a rare human autosomal recessive disorder wit h a wide variety of phenotypic manifestations. AT patients are cancer prone and hypersensitive to ionizing radiation. Cells derived from AT patients r equire higher levels of serum factors, exhibit cytoskeletal defects, and un dergo premature senescence in culture. The gene responsible for AT is ATM ( ataxia-telangiectasia mutated), and its product has been implicated in mito genic signal, transduction, chromosome condensation, meiotic recombination, and cell cycle control. Because of the homology of the human ATM gene to t he TEL1 and rad3 genes of yeast, it has been suggested that mutations in AT M could lead to defective telomere maintenance. The ATM gene product influe nces chromosome end associations, telomere length, and telomere clustering. The defective telomere metabolism in AT cells could be due to altered inte ractions between the telomeres and the nuclear matrix. These interactions w ere studied in nuclear matrix halos before and after irradiation. Altered t elomere-nuclear matrix interactions were observed in cells derived from ind ividuals with AT. AT cells also had different nucleosomal periodicity in th eir telomeres from normal cells. Both telomere-nuclear matrix interactions and nucleosomal periodicity were altered by treatment of primary AT fibrobl asts with ionizing radiation. This effect was not observed in cells derived from normal individuals. A link was also found between altered telomere-nu clear matrix interactions, aberrant telomere clustering, and gonadal atroph y. The telomere defect was not corrected by the ectopic expression of the c atalytic subunit of telomerase (TERT). Since alteration of the yeast telome re chromatin structure is known to influence gene expression, we compared e xpressed sequence tags (ESTs) of Atm-null mouse cells and normal mouse cell s. Several ESTs were found to be aberrantly expressed in Atm-null mouse cel ls. This paper summarizes our recent publications and presents some new dat a on the influence of ATM on telomere metabolism. (C) 2001 by Radiation Res earch Society.