The Bloom's syndrome helicase stimulates the activity of human topoisomerase IIIalpha.
Bloom's syndrome (BS) is a disorder associated with chromosomal instability and a predisposition to the development of cancer. The BS gene product, BLM, is a DNA helicase of the RecQ family that forms a complex in vitro and in vivo with topoisomerase IIIalpha. Here, we show that BLM stimulates the ability of topoisomerase IIIalpha to relax negatively supercoiled DNA. Moreover, DNA binding analyses indicate that BLM recruits topoisomerase IIIalpha to its DNA substrate. Consistent with this, a mutant form of BLM that retains helicase activity, but is unable to bind topoisomerase IIIalpha, fails to stimulate topoisomerase activity. These results indicate that a physical association between BLM and topoisomerase IIIalpha is a prerequisite for their functional biochemical interaction.
Wu
Leonard
L
Cancer Research UK Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK.
Hickson
Ian D
ID
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000378:metabolism; D004278:DNA, Superhelical / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D009154:Mutation; D009690:Nucleic Acid Conformation; D021381:Protein Transport; D053484:RecQ Helicases
D004277:DNA, Single-Stranded; D004278:DNA, Superhelical; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases; D004264:DNA Topoisomerases, Type I