{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T21:04:44Z","timestamp":1761599084128},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2001,3,6]],"date-time":"2001-03-06T00:00:00Z","timestamp":983836800000},"content-version":"vor","delay-in-days":64,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2001,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ataxia telangiectasia (A\u2010T) is a human genetic disorder characterized by progressive cerebellar degeneration, hypersensitivity to ionizing radiation (IR), immunodeficiency, and high cancer risk. At the cellular level, IR sensitivity and increased frequency of spontaneous and IR\u2010induced chromosomal breakage and rearrangements are the hallmarks of A\u2010T. The <jats:italic>ATM<\/jats:italic> gene, mutated in this syndrome, has been cloned and codes for a protein sharing homology with DNA\u2010PKcs, a protein kinase involved in DNA double\u2010strand break (DSB) repair and DNA damage responses. The characteristics of the A\u2010T cellular phenotypes and <jats:italic>ATM<\/jats:italic> gene suggest that ATM may play a role similar to that of DNA\u2010PKcs in DSB repair and that there is a primary DNA repair defect in A\u2010T cells. In the current study, the function of ATM in DNA DSB repair was evaluated in an in vitro system using two plasmids, carrying either an <jats:italic>Eco<\/jats:italic>RI\u2010induced DSB within the <jats:italic>lacZ\u03b1<\/jats:italic> gene or various endonuclease\u2010induced DSB in the <jats:italic>SupF<\/jats:italic> suppressor tRNA gene. We found that the DSB repair efficiency in A\u2010T nuclear extracts was comparable to, if not higher than, that in normal nuclear extracts. However, the repair fidelity in A\u2010T nuclear extracts was decreased when repairing DSB with short 5\u2032 and 3\u2032 overhangs (&lt;4 base pairs (bp)) or blunt ends, but not 5\u2032 4\u2010bp overhangs. Sequencing of the mutant plasmids revealed that deletions involving 1\u20136 nucleotide microhomologies were the major class of mutations in both A\u2010T and normal extracts. However, the size of the deletions in plasmids from A\u2010T nuclear extracts was larger than that from normal nuclear extracts. Expression of the ATM protein in A\u2010T cells corrected the defect in DSB repair in A\u2010T nuclear extracts. These results suggest that ATM plays a role in maintaining genomic stability by preventing the repair of DSB from an error\u2010prone pathway. Environ. Mol. Mutagen. 37:128\u2013140, 2001 \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/em.1020","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T21:43:33Z","timestamp":1030311813000},"page":"128-140","source":"Crossref","is-referenced-by-count":12,"title":["Expression of ATM in ataxia telangiectasia fibroblasts rescues defects in DNA double\u2010strand break repair in nuclear extracts"],"prefix":"10.1002","volume":"37","author":[{"given":"Yuling","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael P.","family":"Carty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory G.","family":"Oakley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael 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