TEL1 from Saccharomyces cerevisiae suppresses chromosome aberrations induced by ionizing radiation in ataxia-telangiectasia cells without affecting cell cycle checkpoints.
The TEL1 gene from Saccharomyces cerevisiae has been shown to be the closest sequence homologue to ATM, the gene mutated in ataxia-telangiectasia (A-T) patients. Functional homology shared between the ATM and Tell proteins has recently been demonstrated based on heterologous expression of the TEL1 gene in human cells derived from A-T patients. TEL1 expression complemented specific cellular A-T deficiencies, i.e. increased radiation-induced apoptosis, telomere shortening and spontaneous hyperrecombination. The mechanism of cellular A-T complementation by TEL1 appears to be independent of p53-dependent signaling cascades, since the deficiency of A-T cells to properly induce p53 upon ionizing radiation was not corrected by TEL1. We now find that the basic number of chromosome aberrations is increased and the number of radiation-induced chromosome aberrations is suppressed in A-T cells upon TEL1 expression. In cell cycle analyses, we find no changes in basic cell cycle distribution or in radiation-induced cell cycle checkpoints following TEL1 expression. We conclude that the radioprotective function of the Tel1 protein includes suppression of apoptosis and suppression of chromosome aberrations, and that both cellular end-points can be uncoupled from ionizing radiation-induced cell cycle checkpoints.
Cao
J P
JP
Soochow University, Suzhou, PR China.
Meyn
M S
MS
Eckardt-Schupp
F
F
Fritz
E
E
D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle; D002869:Chromosome Aberrations; D004307:Dose-Response Relationship, Radiation; D005656:Fungal Proteins / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008957:Models, Genetic; D009154:Mutation; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; D017346:Protein Serine-Threonine Kinases; C513623:TEL1 protein, S cerevisiae