文章：

RecQ解旋酶：多功能基因组看护者

RecQ helicases: multifunctional genome caretakers

原文发布日期：2009-08-06

DOI: 10.1038/nrc2682

类型: Review Article

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要点：

1. RecQ helicases are a highly conserved family and are considered to be genome 'caretakers' that maintain chromosome stability and suppress neoplastic transformation.
2. The crystal structure of RecQ helicases reveals several conserved functional domains. Some of these domains define a particular member of the RecQ helicase family and may be important for functionally distinguishing between the different RecQ helicases expressed in a particular organism.
3. Defects in three of the five human RecQ helicase members give rise to at least five defined disorders associated with cancer predisposition, premature ageing and developmental abnormalities. Mutations in BLM and WRN lead to Bloom's and Werner's syndromes, respectively, and RECQ4 is associated with three distinct disorders: Rothmund–Thomson, RAPADILINO and Baller–Gerold syndromes. These RECQ4 disorders display the common feature of an abnormality in bone development.
4. Mouse models of human RecQ helicase disorders have been generated that partially recapitulate the phenotypes seen in human patients.
5. RecQ helicases possess several biochemical activities and have several important roles in DNA replication and recombination. Some of these activities require or are modulated by physical interactions with other nuclear proteins.
6. BLM is proposed to have roles in mitosis that resolve late-replication intermediates in conjunction with topoisomerase IIIα. Together, these proteins probably function to decatenate entangled DNA that arises during DNA replication.

要点翻译：

1. RecQ解旋酶是一个高度保守的蛋白家族，被视为基因组的"守护者"，能够维持染色体稳定性并抑制肿瘤转化。
2. 该蛋白的晶体结构揭示了数个保守功能结构域。其中某些结构域可界定RecQ解旋酶家族的特异成员，这对区分特定生物体中表达的不同RecQ解旋酶的功能具有重要意义。
3. 人类五种RecQ解旋酶中，有三种酶的缺陷会导致至少五种明确病症，这些疾病与癌症易感性、早衰及发育异常相关。BLM和WRN基因的突变分别引起布鲁姆综合征与沃纳综合征，而RECQ4则与三种疾病相关：罗特蒙德-汤姆森综合征、RAPADILINO综合征和巴勒-杰罗德综合征。这些RECQ4相关疾病共同表现为骨骼发育异常。
4. 科研人员已建立人类RecQ解旋酶疾病的小鼠模型，这些模型部分重现了人类患者的表型特征。
5. RecQ解旋酶具有多种生化活性，在DNA复制与重组过程中发挥重要作用。其中部分活性需要通过与核内其他蛋白质的物理相互作用来实现或受其调节。
6. 研究认为BLM与拓扑异构酶IIIα协同作用，在有丝分裂过程中负责解决晚期复制中间体的问题。这两种蛋白很可能共同作用于解离DNA复制过程中产生的缠结DNA链。

英文摘要：

Around 1% of the open reading frames in the human genome encode predicted DNA and RNA helicases. One highly conserved group of DNA helicases is the RecQ family. Genetic defects in three of the five human RecQ helicases, BLM, WRN and RECQ4, give rise to defined syndromes associated with cancer predisposition, some features of premature ageing and chromosomal instability. In recent years, there has been a tremendous advance in our understanding of the cellular functions of individual RecQ helicases. In this Review, we discuss how these proteins might suppress genomic rearrangements, and therefore function as 'caretaker' tumour suppressors.

摘要翻译： 

人类基因组中约1%的开放阅读框编码预测的DNA和RNA解旋酶。RecQ家族是一类高度保守的DNA解旋酶。五种人类RecQ解旋酶中，BLM、WRN和RECQ4的基因缺陷会导致特定综合征，表现为癌症易感性、部分早衰特征和染色体不稳定性。近年来，我们对单个RecQ解旋酶细胞功能的理解取得了巨大进展。在本综述中，我们讨论这些蛋白如何抑制基因组重排，从而发挥“守护者”型肿瘤抑制因子的作用。

原文链接：

RecQ helicases: multifunctional genome caretakers