Direct association of Bloom's syndrome gene product with the human mismatch repair protein MLH1

Bloom's syndrome (BS) is a rare genetic disorder characterised by genomic i nstability and cancer susceptibility. BLM, the gene mutated in BS, encodes a member of the RecQ family of DNA helicases. Here, we identify hMLH1, whic h is involved in mismatch repair (MMR) and recombination, as a protein that directly interacts with BLM both in vivo and in vitro, and that the two pr oteins co-localise to discrete nuclear foci. The interaction between BLM an d hMLH1 appears to have been evolutionarily conserved, as Sgs1p, the Saccha romyces cerevisiae homologue of BLM, interacts with yeast Mlh1p. However, c ell extracts derived from BS patients show no obvious defects in MMR compar ed to wild-type- and BLM-complemented BS cell extracts. We conclude that th e hMLH1-BLM interaction is not essential for post-replicative MMR, but, mor e likely, is required for some aspect of genetic recombination.