TRF2 recruits the Werner syndrome (WRN) exonuclease for processing of telomeric DNA
TRF2 recruits the Werner syndrome (WRN) exonuclease for processing of telomeric DNA
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DOI：
10.1038/sj.onc.1206906
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发表时间：
2004-01-08
期刊：
影响因子：
8
通讯作者：
Orren, DK
中科院分区：
文献类型：
--
作者：
Machwe, A;Xiao, LR;Orren, DK
易患癌症和过早衰老的Werner综合征是由于WRN基因功能丧失所致。缺乏WRN的细胞表现出基因组的不稳定性，包括端粒异常，并经历过早衰老，表明端粒代谢缺陷。我们发现WRN和TRF2之间的物理和功能相互作用强烈支持这一观点，TRF2是一种对适当的端粒结构至关重要的端粒重复结合因子。TRF2与含有端粒重复序列的DNA底物结合，并通过WRN外切核酸酶活性特异性地促进其降解。WRN和TRF2在没有DNA的情况下也直接相互作用。这些结果表明，TRF2招募WRN在体内的端粒结构的准确加工。因此，我们的发现将端粒维持问题与致癌作用和衰老的特定特征联系起来。
The cancer-prone and premature aging disease Werner syndrome is due to loss of WRN gene function. Cells lacking WRN demonstrate genomic instability, including telomeric abnormalities and undergo premature senescence, suggesting defects in telomere metabolism. This notion is strongly supported by our finding of physical and functional interactions between WRN and TRF2, a telomeric repeat binding factor essential for proper telomeric structure. TRF2 binds to DNA substrates containing telomeric repeats and facilitates their degradation specifically by WRN exonuclease activity. WRN and TRF2 also interact directly in the absence of DNA. These results suggest that TRF2 recruits WRN for accurate processing of telomeric structures in vivo. Thus, our findings link problems in telomere maintenance to both carcinogenesis and specific features of aging.