Defective telomere lagging strand synthesis in cells lacking WRN helicase activity
Defective telomere lagging strand synthesis in cells lacking WRN helicase activity
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DOI：
10.1126/science.1103619
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发表时间：
2004-12-10
期刊：
影响因子：
56.9
通讯作者：
Karlseder, J
中科院分区：
文献类型：
--
作者：
Crabbe, L;Verdun, RE;Karlseder, J
来自沃纳综合征患者的细胞的特征在于缓慢的生长速率、过早衰老、加速的端粒缩短速率和基因组不稳定。该综合征是由RecQ解旋酶WRN的丢失引起的，但潜在的分子机制尚不清楚。在这里，我们报告说，缺乏WRN的细胞表现出从单个姐妹染色单体的端粒缺失。只有端粒复制滞后链合成的影响，防止个别端粒的损失是依赖于WRN的解旋酶活性。端粒酶活性可以抵消端粒的丢失。我们建议，WRN是必要的高效率复制G丰富的端粒DNA，防止端粒功能障碍和随之而来的基因组不稳定。
Cells from Werner syndrome patients are characterized by slow growth rates, premature senescence, accelerated telomere shortening rates, and genome instability. The syndrome is caused by the loss of the RecQ helicase WRN, but the underlying molecular mechanism is unclear. Here we report that cells lacking WRN exhibit deletion of telomeres from single sister chromatids. Only telomeres replicated by lagging strand synthesis were affected, and prevention of loss of individual telomeres was dependent on the helicase activity of WRN. Telomere toss could be counteracted by telomerase activity. We propose that WRN is necessary for efficient replication of G-rich telomeric DNA, preventing telomere dysfunction and consequent genomic instability.