Werner's syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest
Werner's syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest
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DOI：
10.1093/embo-reports/kvd004
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发表时间：
2000-07-01
期刊：
影响因子：
7.7
通讯作者：
West, SC
中科院分区：
文献类型：
--
作者：
Constantinou, A;Tarsounas, M;West, SC
受常染色体隐性遗传疾病维尔纳综合征（WS）影响的个体会出现许多早衰的特征性症状。从WS患者培养的原代成纤维细胞表现出核型异常和复制寿命缩短。WRN基因编码3 '-5' DNA解旋酶，并且是RecQ家族的成员，该家族还包括Bloom综合征基因（BLM）的产物。在这项工作中，我们表明，WRN促进霍利迪路口，一个活动，也表现出BLM的ATP依赖性易位。在被羟基脲阻滞在S期的细胞中，WRN定位于与单链DNA结合蛋白复制蛋白A形成的核灶一致的离散核灶。这些结果与WRN通过解离重组中间体来防止停滞复制叉位点处的异常重组事件的模型一致。
Individuals affected by the autosomal recessive disorder Werner's syndrome (WS) develop many of the symptoms characteristic of premature ageing. Primary fibroblasts cultured from WS patients exhibit karyotypic abnormalities and a reduced replicative life span. The WRN gene encodes a 3'-5' DNA helicase, and is a member of the RecQ family, which also includes the product of the Bloom's syndrome gene (BLM). In this work, we show that WRN promotes the ATP-dependent translocation of Holliday junctions, an activity that is also exhibited by BLM. In cells arrested in S-phase with hydroxyurea, WRN localizes to discrete nuclear foci that coincide with those formed by the single-stranded DNA binding protein replication protein A. These results are consistent with a model in which WRN prevents aberrant recombination events at sites of stalled replication forks by dissociating recombination intermediates.