GENETIC INSTABILITY IN WERNER CELL LINES

产品说明：Werner综合征（WS）是一种常染色体隐性人类遗传疾病，其与遗传不稳定性和癌症风险升高相关。 WS基因（WRN基因座）编码一种163 kDa的蛋白质，该蛋白质是RecQ解旋酶家族的成员。 在拟议的研究中，申请人将测试两个假设：1）WRN解旋酶活性的丧失导致WS的遗传不稳定性;以及2）WRN可以通过确保DNA双链断裂（DSB）的准确修复来限制体内遗传不稳定性。拟议的研究结果将建立WRN解旋酶功能丧失和WS细胞遗传不稳定性之间的因果关系。 该项目与其他项目和Core A一起，旨在确定WRN蛋白在细胞核酸代谢中的功能，以及功能丧失如何促进人体细胞的遗传不稳定性。 研究人员还将提供有关人体细胞DNA双链断裂修复的新信息。

DESCRIPTION: (Applicant's Description) Werner syndrome (WS) is an autosomal recessive human genetic disease that is associated with genetic instability and an elevated risk of cancer. The WS gene (WRN locus) encodes a 163 kDa protein that is a member of the RecQ helicase family. In the proposed research the applicants will test two hypotheses: 1) that the loss of WRN helicase activity causes genetic instability in WS; and 2) that WRN may limit genetic instability in vivo by insuring the accurate repair of DNA double-strand breaks (DSBs). Results of the proposed research will establish a causal link between the loss of WRN helicase function and genetic instability in WS cells. This project, in conjunction with other projects and Core A, aims to identify where the WRN protein functions in cellular nucleic acid metabolism, and how loss of function promotes genetic instability in human somatic cells. The investigators will also provide new information on DNA double-strand break repair in human somatic cells.