Functional link between BLM defective in Bloom's syndrome and the ataxia-telangiectasia-mutated protein, ATM Journal Article
| Authors: | Beamish, H.; Kedar, P.; Kaneko, H.; Chen, P.; Fukao, T.; Peng, C.; Beresten, S.; Gueven, N.; Purdie, D.; Lees-Miller, S.; Ellis, N.; Kondo, N.; Lavin, M. F. |
| Article Title: | Functional link between BLM defective in Bloom's syndrome and the ataxia-telangiectasia-mutated protein, ATM |
| Abstract: | Chromosome aberrations, genomic instability, and cancer predisposition are hallmarks of a number of syndromes in which the defective genes recognize and/or repair DNA damage or are involved in some aspect of DNA processing. We report here direct interaction between BLM, mutated in Bloom's Syndrome (BS), and ATM, mutated is ataxia-telangiectasia, and we have mapped the sites of interaction. Full-length BLM cDNA corrected sister chromatid exchange (SCE) and radiosensitivity in BS cells. Mitotic phosphorylation of BLM was partially dependent on ATM, and phosphorylation sites on BLM were identified. A phosphospecific antibody against one of these sites (Thr-99) revealed radiation-induced phosphorylation, which was defective in ataxia-telangiectasia cells. Stable cell lines expressing phosphorylation site mutants failed to correct radiosensitivity in BS cells but corrected SCE. These mutants also sensitized normal control cells to radiation and increased radiation-induced chromosome aberrations but did not cause SCE numbers to increase. These data suggest that ATM and BLM function together in recognizing abnormal DNA structures by direct interaction and that these phosphorylation sites in BLM are important for radiosensitivity status but not for SCE frequency. |
| Keywords: | controlled study; protein phosphorylation; gene mutation; human cell; dna-binding proteins; mitosis; proteins; cell cycle proteins; dna damage; cell survival; cancer susceptibility; genes; gene expression; radiation; phosphorylation; chromosome aberration; dna; protein-serine-threonine kinases; tumor suppressor proteins; glutathione transferase; atm protein; radiosensitivity; sister chromatid exchange; biochemistry; fluorescence activated cell sorting; ataxia; adenosine triphosphatases; mutagenesis; dna helicases; complementary dna; ataxia telangiectasia; radiation tolerance; bloom syndrome; precipitin tests; humans; human; priority journal; article |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 277 |
| Issue: | 34 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2002-08-23 |
| Start Page: | 30515 |
| End Page: | 30523 |
| Language: | English |
| DOI: | 10.1074/jbc.M203801200 |
| PUBMED: | 12034743 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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