Nucleic Acids Research, 2002, Vol. 30, No. 22 4823-4829
© 2002 Oxford University Press
The Bloom’s syndrome helicase stimulates the activity of human topoisomerase III
Cancer Research UK Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK
*To whom correspondence should be addressed. Tel: +44 1865 222 417; Fax: +44 1865 222 431; Email: ian.hickson{at}cancer.org.uk
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 III
. Here, we show that BLM stimulates the ability of topoisomerase III to relax negatively supercoiled DNA. Moreover, DNA binding analyses indicate that BLM recruits topoisomerase III to its DNA substrate. Consistent with this, a mutant form of BLM that retains helicase activity, but is unable to bind topoisomerase III, fails to stimulate topoisomerase activity. These results indicate that a physical association between BLM and topoisomerase III is a prerequisite for their functional biochemical interaction.
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