title: Point mutations causing Bloom's syndrome abolish ATPase and DNA helicase activities of the BLM protein.
abstract: Bloom's syndrome (BS) is a rare human genetic disorder characterized by mutations within the BLM gene whose primary effects are excessive chromosome breakage and increased rates of sister chromatid interchange in somatic cells. We report the characterization of a murine protein (mBLM), highly related to the product of the human BLM gene. This protein exhibits an ATP-dependent DNA-helicase activity that unwinds DNA in a 3'-5' direction. Single amino acid substitutions found in BS cells, abolish both ATPase and helicase activities of this protein, indicating that defects in these BLM functions may be primarily responsible for BS establishment. These results provide the first evidence suggesting that the enzymatic activities of the BLM product are implicated in the upholding of genomic integrity.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM/CNRS/ULP, BP163, C.U. de Strasbourg, France.
authors.forename: A
authors.initials: A
authors.lastname: Bahr
authors.forename: F
authors.initials: F
authors.lastname: De Graeve
authors.forename: C
authors.initials: C
authors.lastname: Kedinger
authors.forename: B
authors.initials: B
authors.lastname: Chatton
mesh_terms: D051696:Activating Transcription Factors; D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D001816:Bloom Syndrome / Q000201:enzymology / Q000235:genetics*; D019556:COS Cells; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D004265:DNA Helicases / Q000737:chemistry / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D051379:Mice / Q000235:genetics*; D008969:Molecular Sequence Data; D017354:Point Mutation; D053484:RecQ Helicases; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D014898:Werner Syndrome / Q000201:enzymology / Q000235:genetics
chemical_list: D051696:Activating Transcription Factors; D001798:Blood Proteins; D018076:DNA, Complementary; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; C506725:RECQL protein, human; D004265:DNA Helicases; D053484:RecQ Helicases