Functional link between BLM defective in Bloom's syndrome and the ataxia-telangiectasia-mutated protein, ATM

Beamish, Heather, Kedar, Padmini, Kaneko, Hideo, Chen, Philip, Fukao, Toshiyuki, Peng, Cheng, Beresten, Sergei, Gueven, Nuri, Purdie, David, Lees-Miller, Susan, Ellis, Nathan, Kondo, Naomi and Lavin, Martin F. (2002) Functional link between BLM defective in Bloom's syndrome and the ataxia-telangiectasia-mutated protein, ATM. Journal of Biological Chemistry, 277 34: 30515-30523. doi:10.1074/jbc.M203801200

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ115468_OA.pdf Full text (open access) application/pdf 334.11KB 0

Author Beamish, Heather
Kedar, Padmini
Kaneko, Hideo
Chen, Philip
Fukao, Toshiyuki
Peng, Cheng
Beresten, Sergei
Gueven, Nuri
Purdie, David
Lees-Miller, Susan
Ellis, Nathan
Kondo, Naomi
Lavin, Martin F.
Title Functional link between BLM defective in Bloom's syndrome and the ataxia-telangiectasia-mutated protein, ATM
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2002-01-01
Sub-type Article (original research)
DOI 10.1074/jbc.M203801200
Open Access Status File (Publisher version)
Volume 277
Issue 34
Start page 30515
End page 30523
Total pages 9
Place of publication Bethesda
Publisher Amer Soc Biochemistry Molecular Biology Inc
Language eng
Subject 320000 Medical and Health Sciences
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.
Keyword Biochemistry & Molecular Biology
Nijmegen Breakage Syndrome
Dna-damage Response
S-phase
Syndrome Cells
Syndrome Gene
Dependent Phosphorylation
Ionizing-radiation
Checkpoint Pathway
Positional Cloning
Nuclear-structure
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 90 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 92 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 17 Oct 2007, 21:30:00 EST