title: ATM-dependent phosphorylation and accumulation of endogenous BLM protein in response to ionizing radiation.
abstract: Bloom's syndrome (BS), a rare genetic disease, arises through mutations in both alleles of the BLM gene which encodes a 3'-5' DNA helicase identified as a member of the RecQ family. BS patients exhibit a high predisposition to development of all types of cancer affecting the general population and BLM-deficient cells display a strong genetic instability. We recently showed that BLM protein expression is regulated during the cell cycle, accumulating to high levels in S phase, persisting in G2/M and sharply declining in G1, suggesting a possible implication of BLM in a replication (S phase) and/or post-replication (G2 phase) process. Here we show that, in response to ionizing radiation, BLM-deficient cells exhibit a normal p53 response as well as an intact G1/S cell cycle checkpoint, which indicates that ATM and p53 pathways are functional in BS cells. We also show that the BLM defect is associated with a partial escape of cells from the gamma-irradiation-induced G2/M cell cycle checkpoint. Finally, we present data demonstrating that, in response to ionizing radiation, BLM protein is phosphorylated and accumulates through an ATM-dependent pathway. Altogether, our data indicate that BLM participates in the cellular response to ionizing radiation by acting as an ATM kinase downstream effector.
authors.affiliation: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 1598, Institut Gustave Roussy, Villejuif, France.
authors.forename: M
authors.initials: M
authors.lastname: Ababou
authors.forename: S
authors.initials: S
authors.lastname: Dutertre
authors.forename: Y
authors.initials: Y
authors.lastname: Lécluse
authors.forename: R
authors.initials: R
authors.lastname: Onclercq
authors.forename: B
authors.initials: B
authors.lastname: Chatton
authors.forename: M
authors.initials: M
authors.lastname: Amor-Guéret
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D064007:Ataxia Telangiectasia Mutated Proteins; D001816:Bloom Syndrome / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D002453:Cell Cycle / Q000528:radiation effects*; D018797:Cell Cycle Proteins; D002461:Cell Line, Transformed; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D005720:Gamma Rays; D017353:Gene Deletion; D006801:Humans; D007700:Kinetics; D008938:Mitosis / Q000187:drug effects; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation / Q000528:radiation effects; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D053484:RecQ Helicases; D016196:S Phase / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D010744:Phosphoric Monoester Hydrolases; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)