title: Characterization of a new BLM mutation associated with a topoisomerase II alpha defect in a patient with Bloom's syndrome.
abstract: Bloom's syndrome (BS), a human recessive disorder associated with an increased risk of malignancy, arises through mutations in both alleles of the BLM gene, which was recently identified as a member of the RecQ helicase family. BS cells are characterized by an increased rate of sister chromatid exchange (SCE). However, a subpopulation of lymphocytes exhibiting a normal level of SCE is observed in some patients. It has been proposed that reversion to a low-SCE phenotype involves an intragenic crossing over between the paternal and maternal BLM alleles, generating a wild-type allele. In this study we characterize a new BLM mutation in a BS patient leading to the replacement, in the C-terminal region of Blm, of a highly conserved cysteine by a phenylalanine in codon 1036. Moreover, our data show that this patient also inherited a BLM allele carrying a mutation affecting its expression and that a somatic intragenic crossing over was involved in reversion to the low-SCE phenotype. Further, we show that both topoisomerase II alpha mRNA and protein levels are decreased in the high-SCE cells derived from this patient, whereas they are normal in the corresponding low-SCE cells. Altogether, our data led us to propose that besides its putative helicase activity, Blm could be involved in transcription regulation.
authors.affiliation: Laboratoire de Génétique Moleculaire et Cancérogenèse, Institut d'Oncologie Cellulaire et Moléculaire Humaine, Bobigny, France.
authors.forename: F
authors.initials: F
authors.lastname: Foucault
authors.forename: C
authors.initials: C
authors.lastname: Vaury
authors.forename: A
authors.initials: A
authors.lastname: Barakat
authors.forename: D
authors.initials: D
authors.lastname: Thibout
authors.forename: P
authors.initials: P
authors.lastname: Planchon
authors.forename: C
authors.initials: C
authors.lastname: Jaulin
authors.forename: F
authors.initials: F
authors.lastname: Praz
authors.forename: M
authors.initials: M
authors.lastname: Amor-Guéret
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm; D001816:Bloom Syndrome / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics*; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004268:DNA-Binding Proteins; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D053484:RecQ Helicases; D016415:Sequence Alignment
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases; D004250:DNA Topoisomerases, Type II