The DNA helicase activity of BLM is necessary for the correction of the genomic instability of Bloom syndrome cells

Bloom syndrome (BS) is a rare autosomal recessive disorder characterized by growth deficiency, immunodeficiency, genomic instability, and the early de velopment of cancers of many types. BLM, the protein encoded by BLM, the ge ne mutated in BS, is localized in nuclear foci and absent from BS cells. BL M encodes a DNA helicase, and proteins from three missense alleles lack dis placement activity. BLM transfected into BS cells reduces the frequency of sister chromatid exchanges and restores BLM in the nucleus. Missense allele s fail to reduce the sister chromatid exchanges in transfected BS cells or restore the normal nuclear pattern. BLM complements a phenotype of a Saccha romyces cerevisiae sgs1 top3 strain, and the missense alleles do not. This work demonstrates the importance of the enzymatic activity of BLM for its f unction and nuclear localization pattern.