Furuichi Y
AGENE Research Institute, Kamakura, Japan.
Ann N Y Acad Sci. 2001 Apr;928:121-31. doi: 10.1111/j.1749-6632.2001.tb05642.x.
DNA helicases, because they unwind duplex DNA, have important roles in cellular DNA events such as replication, recombination, repair, and transcription. Multiple DNA helicase families with seven consensus motifs have been found, and members within each helicase family also share sequence homologies between motifs. The RecQ helicase family includes helicases that have extensive amino acid sequence homologies to the E. coli DNA helicase RecQ, which has been implicated in double-strand break repair and suppression of illegitimate recombination. To date, five RecQ helicase species exist in humans, but their exact biological functions remain unknown. In this paper, on the basis of five years of work, I overview the updated molecular biology of five human RecQ helicases; genetic diseases such as Werner's, Bloom's, and Rothmund-Thomson's syndromes caused by helicase mutations; the associated premature aging phenotype; and an increased risk of neoplasms. I also describe a hypothesis of "tissue-specific genomic instability" that accounts for the pathology behind multisymptomatic RecQ helicase syndromes.
DNA解旋酶由于能解开双链DNA，在细胞DNA事件如复制、重组、修复和转录中发挥着重要作用。已发现多个具有七个共有基序的DNA解旋酶家族，每个解旋酶家族的成员在基序之间也具有序列同源性。RecQ解旋酶家族包括与大肠杆菌DNA解旋酶RecQ具有广泛氨基酸序列同源性的解旋酶，RecQ与双链断裂修复和抑制非法重组有关。迄今为止，人类中存在五种RecQ解旋酶，但它们的确切生物学功能仍不清楚。在本文中，基于五年的研究工作，我概述了五种人类RecQ解旋酶的最新分子生物学；由解旋酶突变引起的诸如沃纳综合征、布卢姆综合征和罗思蒙德 - 汤姆森综合征等遗传疾病；相关的早衰表型；以及肿瘤发生风险增加。我还描述了一种“组织特异性基因组不稳定性”假说，该假说解释了多症状RecQ解旋酶综合征背后的病理学。
