Wu Leonard, Hickson Ian D
Cancer Research UK Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK.
Nucleic Acids Res. 2002 Nov 15;30(22):4823-9. doi: 10.1093/nar/gkf611.
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.
布卢姆综合征（BS）是一种与染色体不稳定以及易患癌症相关的疾病。BS基因产物BLM是RecQ家族的一种DNA解旋酶，它在体外和体内都能与拓扑异构酶IIIα形成复合物。在此，我们表明BLM能刺激拓扑异构酶IIIα使负超螺旋DNA松弛的能力。此外，DNA结合分析表明BLM将拓扑异构酶IIIα招募到其DNA底物上。与此一致的是，一种保留解旋酶活性但无法结合拓扑异构酶IIIα的BLM突变形式不能刺激拓扑异构酶活性。这些结果表明BLM与拓扑异构酶IIIα之间的物理关联是它们功能性生化相互作用的先决条件。
