Bloom helicase and DNA topoisomerase IIIalpha are involved in the dissolution of sister chromatids.
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.
Seki
Masayuki
M
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
Nakagawa
Takayuki
T
Seki
Takahiko
T
Kato
Genta
G
Tada
Shusuke
S
Takahashi
Yuriko
Y
Yoshimura
Akari
A
Kobayashi
Takayuki
T
Aoki
Ayako
A
Otsuki
Makoto
M
Habermann
Felix A
FA
Tanabe
Hideyuki
H
Ishii
Yutaka
Y
Enomoto
Takemi
T
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
D007527:Isoenzymes; D015075:2-Aminopurine; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases; D004264:DNA Topoisomerases, Type I