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The Bloom's Syndrome Gene Product Interacts with Topoisomerase III*

Leonard Wu,S. Davies,P. North,H. Goulaouic,J. Riou,H. Turley,K. Gatter,I. Hickson

Published 2000 in Journal of Biological Chemistry

ABSTRACT

Bloom's syndrome is a rare genetic disorder associated with loss of genomic integrity and a large increase in the incidence of many types of cancer at an early age. The Bloom's syndrome gene product, BLM, belongs to the RecQ family of DNA helicases, which also includes the human Werner's and Rothmund-Thomson syndrome gene products and the Sgs1 protein of Saccharomyces cerevisiae. This family shows strong evolutionary conservation of protein structure and function. Previous studies have shown that Sgs1p interacts both physically and genetically with topoisomerase III. Here, we have investigated whether this interaction has been conserved in human cells. We show that BLM and hTOPO IIIα, one of two human topoisomerase III homologues, co-localize in the nucleus of human cells and can be co-immunoprecipitated from human cell extracts. Moreover, the purified BLM and hTOPO IIIα proteins are able to bind specifically to each other in vitro, indicating that the interaction is direct. We have mapped two independent domains on BLM that are important for mediating the interaction with hTOPO IIIα. Furthermore, through characterizing a genetic interaction betweenBLM and TOP3 in S. cerevisiae, we have identified a functional role for the hTOPO IIIα interaction domains in BLM.

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