Oshima Junko, Sidorova Julia M, Monnat Raymond J
Department of Pathology, University of Washington, Seattle, WA 98195, USA; Department of Medicine, Chiba University, Chiba, Japan.
Department of Pathology, University of Washington, Seattle, WA 98195, USA.
Ageing Res Rev. 2017 Jan;33:105-114. doi: 10.1016/j.arr.2016.03.002. Epub 2016 Mar 15.
Werner syndrome (WS) is a prototypical segmental progeroid syndrome characterized by multiple features consistent with accelerated aging. It is caused by null mutations of the WRN gene, which encodes a member of the RECQ family of DNA helicases. A unique feature of the WRN helicase is the presence of an exonuclease domain in its N-terminal region. Biochemical and cell biological studies during the past decade have demonstrated involvements of the WRN protein in multiple DNA transactions, including DNA repair, recombination, replication and transcription. A role of the WRN protein in telomere maintenance could explain many of the WS phenotypes. Recent discoveries of new progeroid loci found in atypical Werner cases continue to support the concept of genomic instability as a major mechanism of biological aging. Based on these biological insights, efforts are underway to develop therapeutic interventions for WS and related progeroid syndromes.
沃纳综合征（WS）是一种典型的节段性早老综合征，其特征是具有多种与加速衰老相符的特征。它由WRN基因的无效突变引起，该基因编码DNA解旋酶RECQ家族的一员。WRN解旋酶的一个独特特征是其N端区域存在一个核酸外切酶结构域。过去十年的生化和细胞生物学研究表明，WRN蛋白参与了多种DNA事务，包括DNA修复、重组、复制和转录。WRN蛋白在端粒维持中的作用可以解释许多WS表型。最近在非典型沃纳病例中发现的新的早老基因座继续支持基因组不稳定是生物衰老主要机制的概念。基于这些生物学见解，目前正在努力开发针对WS和相关早老综合征的治疗干预措施。
