The Bloom's syndrome helicase stimulates the activity of human topoisomerase IIIα

Abstract

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 IIIα. Here, we show that BLM stimulates the ability of topoisomerase IIIα to relax negatively supercoiled DNA. Moreover, DNA binding analyses indicate that BLM recruits topoisomerase IIIα to its DNA substrate. Consistent with this, a mutant form of BLM that retains helicase activity, but is unable to bind topoisomerase IIIα, fails to stimulate topoisomerase activity. These results indicate that a physical association between BLM and topoisomerase IIIα is a prerequisite for their functional biochemical interaction.