Bahr A, De Graeve F, Kedinger C, Chatton B
Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM/CNRS/ULP, BP163, C.U. de Strasbourg, France.
Oncogene. 1998 Nov 19;17(20):2565-71. doi: 10.1038/sj.onc.1202389.
Bloom's syndrome (BS) is a rare human genetic disorder characterized by mutations within the BLM gene whose primary effects are excessive chromosome breakage and increased rates of sister chromatid interchange in somatic cells. We report the characterization of a murine protein (mBLM), highly related to the product of the human BLM gene. This protein exhibits an ATP-dependent DNA-helicase activity that unwinds DNA in a 3'-5' direction. Single amino acid substitutions found in BS cells, abolish both ATPase and helicase activities of this protein, indicating that defects in these BLM functions may be primarily responsible for BS establishment. These results provide the first evidence suggesting that the enzymatic activities of the BLM product are implicated in the upholding of genomic integrity.
布卢姆综合征（BS）是一种罕见的人类遗传疾病，其特征是BLM基因突变，主要影响是体细胞中染色体过度断裂和姐妹染色单体交换率增加。我们报告了一种与人类BLM基因产物高度相关的小鼠蛋白（mBLM）的特性。这种蛋白表现出一种依赖ATP的DNA解旋酶活性，能沿3'-5'方向解开DNA。在BS细胞中发现的单个氨基酸取代消除了该蛋白的ATP酶和解旋酶活性，表明这些BLM功能缺陷可能是BS发病的主要原因。这些结果提供了首个证据，表明BLM产物的酶活性与维持基因组完整性有关。
