Ozgenc A, Loeb L A
The Joseph Gottstein Memorial Cancer Research Laboratory, Department of Pathology, University of Washington, Seattle, Wash., USA.
Genome Dyn. 2006;1:206-217. doi: 10.1159/000092509.
Werner syndrome (WS) is a rare autosomal recessive genetic instability/cancer predisposition disorder that displays many symptoms of premature aging. The mimicry of agerelated phenotypes in WS, as well as its dependence on a single defective gene product, has provided the impetus for studying this fascinating disease as a model system for normative aging and its related pathologies such as atherosclerosis, neoplasia, diabetes mellitus, and osteoporosis. The gene product defective in WS, WRN, is a member of the RecQ DNA helicase family that is widely distributed in all kingdoms of life, and is believed to play a central role in genomic stability by preferentially operating on non-canonical DNA structures. Although there have been considerable advances in our understanding of the biochemistry of WRN and its interacting protein partners, the in vivo molecular function(s) of WRN remain(s) elusive. In addition to summarizing the features and clinical progression of WS, the following chapter details our current understanding of the WRN protein with respect to its biochemistry and its interacting protein partners, and considers its putative in vivo roles in various DNA transactions.
沃纳综合征（WS）是一种罕见的常染色体隐性遗传不稳定性/癌症易感性疾病，表现出许多早衰症状。WS中与年龄相关表型的模仿，以及其对单一缺陷基因产物的依赖性，为将这种迷人的疾病作为正常衰老及其相关病理（如动脉粥样硬化、肿瘤形成、糖尿病和骨质疏松症）的模型系统进行研究提供了动力。WS中缺陷的基因产物WRN是RecQ DNA解旋酶家族的成员，广泛分布于所有生物界，并且被认为通过优先作用于非经典DNA结构在基因组稳定性中发挥核心作用。尽管我们对WRN及其相互作用的蛋白质伙伴的生物化学有了相当大的进展，但WRN在体内的分子功能仍然难以捉摸。除了总结WS的特征和临床进展外，以下章节详细介绍了我们目前对WRN蛋白在其生物化学及其相互作用的蛋白质伙伴方面的理解，并考虑了其在各种DNA交易中假定的体内作用。
