title: Bloom helicase and DNA topoisomerase IIIalpha are involved in the dissolution of sister chromatids.
abstract: Bloom's syndrome (BS) is an autosomal disorder characterized by predisposition to a wide variety of cancers. The gene product whose mutation leads to BS is the RecQ family helicase BLM, which forms a complex with DNA topoisomerase IIIalpha (Top3alpha). However, the physiological relevance of the interaction between BLM and Top3alpha within the cell remains unclear. We show here that Top3alpha depletion causes accumulation of cells in G2 phase, enlargement of nuclei, and chromosome gaps and breaks that occur at the same position in sister chromatids. The transition from metaphase to anaphase is also inhibited. All of these phenomena except cell lethality are suppressed by BLM gene disruption. Taken together with the biochemical properties of BLM and Top3alpha, these data indicate that BLM and Top3alpha execute the dissolution of sister chromatids.
authors.affiliation: Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba 6-3, Aramaki, Aoba-ku, Sendai 980-8578, Japan. seki@mail.pharm.tohoku.ac.jp
authors.forename: Masayuki
authors.initials: M
authors.lastname: Seki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Takahiko
authors.initials: T
authors.lastname: Seki
authors.forename: Genta
authors.initials: G
authors.lastname: Kato
authors.forename: Shusuke
authors.initials: S
authors.lastname: Tada
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Akari
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Ayako
authors.initials: A
authors.lastname: Aoki
authors.forename: Makoto
authors.initials: M
authors.lastname: Otsuki
authors.forename: Felix A
authors.initials: FA
authors.lastname: Habermann
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Tanabe
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Ishii
authors.forename: Takemi
authors.initials: T
authors.lastname: Enomoto
mesh_terms: D015075:2-Aminopurine / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000705:Anaphase / Q000187:drug effects; D000818:Animals; D017209:Apoptosis; D002645:Chickens; D002842:Chromatids / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics*; D002869:Chromosome Aberrations; D004265:DNA Helicases / Q000378:metabolism*; D004264:DNA Topoisomerases, Type I / Q000172:deficiency / Q000378:metabolism*; D016195:G2 Phase / Q000187:drug effects; D018390:Gene Targeting; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008677:Metaphase / Q000187:drug effects; D051379:Mice; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D053484:RecQ Helicases
chemical_list: D007527:Isoenzymes; D015075:2-Aminopurine; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases; D004264:DNA Topoisomerases, Type I