Objective Bloom’s syndrome is an autosomal recessive disorder characterized by genomic instability and a predisposition to many cancers. Mutations of the BLM gene (encoding a BLM helicase) may form a structure of the etiology of this disease. As a global pollutant, mercury poses a major threat to human health. The current study was conducted to elucidate the effects of Hg 2+ on the structure and activity of BLM642‐1290 recombinant helicase, and to further explore the molecular mechanisms of mercury toxicity to the DNA helicase. Methods The effects of Hg 2+ on biological activity and structure of BLM642‐1290 recombinant helicase were determined by fluorescence polarized, ultraviolet spectroscopic, and free‐phosphorus assay technologies, respectively. Results The helicase activity, the DNA‐binding activity, and the ATPase activity of BLM642‐1290 recombinant helicase were inhibited by Hg 2+ treatment. The LMCT (ligand‐to‐metal charge transition) peaks of the helicase were enhanced with the increase of the Hg 2+ level. The LMCT peaks of the same concentration of helicase gradually increased over time. Conclusions The biological activity of BLM642‐1290 recombinant helicase is inhibited by Hg 2+ treatment. The conformation of the helicase is significantly altered by Hg 2+ . There exist two binding sites between Hg 2+ and the helicase, which are located in the amino acid residues 1063‐1066 and 940‐944 of the helicase, respectively. Objective Bloom’s syndrome is an autosomal recessive disorder characterized by genomic instability and a predisposition to many cancers. Mutations of the BLM gene (encoding a BLM helicase) may form a structure of the etiology of this disease. As a global pollutant, mercury poses a major The current study was conducted to elucidate the effects of Hg 2+ on the structure and activity of BLM642-1290 recombinant helicase, and to further explore the molecular mechanisms of mercury toxicity to the DNA helicase. Methods The effects of Hg 2+ on biological activity and structure of BLM642-1290 recombinant helicase were determined by fluorescence polarized, ultraviolet spectroscopic, and free-phosphorus assay technologies, respectively. Results The helicase activity, the DNA-binding activity, and the ATPase activity of BLM642-1290 recombinant helicase were inhibited by Hg 2+ treatment. The LMCT (ligand-to-metal charge transition) peaks of the helicase were en Concurrent The biological activity of BLM642-1290 recombinant helicase is inhibited by Hg 2+ treatment. The conformation of the helicase is significantly higher than the Hg 2+ level. altered by Hg 2+. There exist two binding sites between Hg 2+ and the helicase, which are located in the amino acid residues 1063-1066 and 940-944 of the helicase, respectively.