Evolution of the RECQ family of helicases: A drosophila homolog, Dmblm, is similar to the human bloom syndrome gene.
Evolution of the RECQ family of helicases: A drosophila homolog, Dmblm, is similar to the human bloom syndrome gene.
复制标题
DOI：
10.1093/genetics/151.3.1027
复制
发表时间：
1999-03
期刊：
影响因子：
3.3
通讯作者：
Kohji Kusano;M. Berres;William R. Engels
中科院分区：
文献类型：
--
作者：
Kohji Kusano;M. Berres;William R. Engels
已经发现了大肠杆菌RecQ DNA解旋酶的几个真核同源物，其中包括人类BLM基因，其突变导致布卢姆综合征，以及人类WRN基因，其突变导致类似过早衰老的沃纳综合征。我们克隆了一个果蝇同源的RECQ解旋酶家族，Dmblm（果蝇Bloom），它编码一个假定的1487个氨基酸的蛋白质。系统发育和点图分析RECQ家族，包括10个真核生物和3个原核生物的基因，表明Dmblm是最密切相关的智人BLM基因，表明功能相似。此外，我们发现，Dmblm cDNA部分挽救了酿酒酵母sgs 1突变体的甲基甲磺酸盐的敏感性，证明了Dmblm和SGS 1之间的功能相似性的存在。我们的分析确定了RECQ家族中的四个可能的亚家族：（1）BLM亚家族（H。sapiens Bloom，D.黑腹小杆线虫Dmblm和秀丽隐杆线虫T04A11.6）;（2）酵母RECQ亚群（S.酿酒酵母SGS 1和粟酒裂殖酵母rqh 1/rad 12）; sapiens RECQL/Q1和C. elegans K02F3.1）;（4）WRN亚群（H. sapiens Werner和C. elegans F18C5.2）。这一结果可能表明，后生动物持有至少三个RECQ基因，其中每一个可能有不同的功能，多个RECQ基因分化的多细胞生物体的产生。我们建议，无脊椎动物，如线虫和昆虫是有用的人类遗传疾病的模型系统。
Several eukaryotic homologs of the Escherichia coli RecQ DNA helicase have been found. These include the human BLM gene, whose mutation results in Bloom syndrome, and the human WRN gene, whose mutation leads to Werner syndrome resembling premature aging. We cloned a Drosophila melanogaster homolog of the RECQ helicase family, Dmblm (Drosophila melanogaster Bloom), which encodes a putative 1487-amino-acid protein. Phylogenetic and dot plot analyses for the RECQ family, including 10 eukaryotic and 3 prokaryotic genes, indicate Dmblm is most closely related to the Homo sapiens BLM gene, suggesting functional similarity. Also, we found that Dmblm cDNA partially rescued the sensitivity to methyl methanesulfonate of Saccharomyces cerevisiae sgs1 mutant, demonstrating the presence of a functional similarity between Dmblm and SGS1. Our analyses identify four possible subfamilies in the RECQ family: (1) the BLM subgroup (H. sapiens Bloom, D. melanogaster Dmblm, and Caenorhabditis elegans T04A11.6); (2) the yeast RECQ subgroup (S. cerevisiae SGS1 and Schizosaccharomyces pombe rqh1/rad12); (3) the RECQL/Q1 subgroup (H. sapiens RECQL/Q1 and C. elegans K02F3.1); and (4) the WRN subgroup (H. sapiens Werner and C. elegans F18C5.2). This result may indicate that metazoans hold at least three RECQ genes, each of which may have a different function, and that multiple RECQ genes diverged with the generation of multicellular organisms. We propose that invertebrates such as nematodes and insects are useful as model systems of human genetic diseases.