The Bloom's syndrome protein (BLM) interacts with MLH1 but is not requiredfor DNA mismatch repair

Bloom's syndrome (BS) is a rare autosomal recessive disorder characterized by pre- and postnatal growth deficiency, immunodeficiency, and a tremendous predisposition to a wide variety of cancers. Cells from BS individuals are characterized by a high incidence of chromosomal gaps and breaks, elevated sister chromatid exchange, quadriradial formations, and locus-specific mut ations. BS is the consequence of mutations that lead to loss of function of BLM, a gene encoding a helicase with homology to the RecQ helicase family. To delineate the role of BLM in DNA replication, recombination, and repair we used a yeast two-hybrid screen to identify potential protein partners o f the BLM helicase. The C terminus of BLM interacts directly with MLH1 in t he yeast-two hybrid assay; far Western analysis and co-immunoprecipitations confirmed the interaction. Cell extracts deficient in BLM were competent f or DNA mismatch repair. These data suggest that the BLM helicase and MLH1 f unction together in replication, recombination, or DNA repair events indepe ndent of single base mismatch repair.