Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases
Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases
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DOI：
10.1074/jbc.m205396200
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发表时间：
2002-10-25
影响因子：
4.8
通讯作者：
Bohr, VA
中科院分区：
文献类型：
--
作者：
Opresko, PL;von Kobbe, C;Bohr, VA
维尔纳综合征是一种人类早衰疾病，表现出与端粒维持相关的细胞缺陷，包括基因组不稳定、过早衰老和端粒加速侵蚀。Werner蛋白（WRN）的酵母同源物Sgs1是端粒酶缺陷细胞中重组介导的端粒延长所必需的。在人类细胞中，我们报道了WRN共定位并与关键的端粒维持蛋白TRF2物理相互作用。这种相互作用是由WRN的RecQ保守G端区介导的。在体外，TRF2显示出对WRN和另一个RecQ家族成员Bloom综合征蛋白（BLM）的高亲和力。TRF2与WRN或BLM相互作用可显著刺激其解旋酶活性。此外，WRN和BLM解旋酶与复制蛋白A合作，主动解开TRF2预结合的长端粒双工区域。这些结果表明，TRF2与WRN（可能还有BLM）在端粒末端的共同途径中起作用。
Werner syndrome is a human premature aging disorder displaying cellular defects associated with telomere maintenance including genomic instability, premature senescence, and accelerated telomere erosion. The yeast homologue of the Werner protein (WRN), Sgs1, is required for recombination-mediated lengthening of telomeres in telomerase-deficient cells. In human cells, we report that WRN co-localizes and physically interacts with the critical telomere maintenance protein TRF2. This interaction is mediated by the RecQ conserved G terminal region of WRN. In vitro, TRF2 demonstrates high affinity for WRN and for another RecQ family member, the Bloom syndrome protein (BLM). TRF2 interaction with either WRN or BLM results in a notable stimulation of their helicase activities. Furthermore, the WRN and BLM helicases, partnered with replication protein A, actively unwind long telomeric duplex regions that are pre-bound by TRF2. These results suggest that TRF2 functions with WRN, and possibly BLM, in a common pathway at telomeric ends.