Strand exchange of telomeric DNA catalyzed by the Werner syndrome protein (WRN) is specifically stimulated by TRF2.
Strand exchange of telomeric DNA catalyzed by the Werner syndrome protein (WRN) is specifically stimulated by TRF2.
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DOI：
10.1093/nar/gku454
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发表时间：
2014-07
影响因子：
14.9
通讯作者：
Machwe A
中科院分区：
文献类型：
--
作者：
Edwards DN;Orren DK;Machwe A
沃纳综合征 (WS) 是由 RecQ 解旋酶 WRN 功能丧失引起的，是一种以过早衰老和癌症发病率升高为特征的遗传性疾病。 WRN 具有 DNA 结合、核酸外切酶、ATP 酶、解旋酶和链退火活性，表明其在重组相关过程中可能发挥作用。有证据表明，WRN 缺陷会导致端粒异常，这可能是 WS 早期出现衰老表型的基础。此外，TRF2（一种端粒保护所必需的蛋白质）与 WRN 相互作用并影响其基本解旋酶和核酸外切酶活性。然而，这些研究并没有深入了解 WRN 在端粒上的具体功能。在这里，我们探讨了 WRN 和 TRF2 在端粒重组过程中合作的可能性。我们的结果表明，TRF2 通过与 WRN 和端粒 DNA 相互作用，刺激 WRN 介导的链交换，特别是端粒底物之间的链交换。 TRF2 的基本结构域对于这种刺激尤其重要。尽管 TRF1 以相似的亲和力结合端粒 DNA，但它对 WRN 介导的端粒 DNA 链交换影响极小。此外，TRF2 被 WRN 从端粒 DNA 中取代，与其 ATP 酶和解旋酶活性无关。总之，这些结果表明 TRF2 和 WRN 在端粒重组过程中协调作用，这与与 WRN 功能改变相关的某些端粒异常一致。
Werner syndrome (WS), caused by loss of function of the RecQ helicase WRN, is a hereditary disease characterized by premature aging and elevated cancer incidence. WRN has DNA binding, exonuclease, ATPase, helicase and strand annealing activities, suggesting possible roles in recombination-related processes. Evidence indicates that WRN deficiency causes telomeric abnormalities that likely underlie early onset of aging phenotypes in WS. Furthermore, TRF2, a protein essential for telomere protection, interacts with WRN and influences its basic helicase and exonuclease activities. However, these studies provided little insight into WRN's specific function at telomeres. Here, we explored the possibility that WRN and TRF2 cooperate during telomeric recombination processes. Our results indicate that TRF2, through its interactions with both WRN and telomeric DNA, stimulates WRN-mediated strand exchange specifically between telomeric substrates; TRF2's basic domain is particularly important for this stimulation. Although TRF1 binds telomeric DNA with similar affinity, it has minimal effects on WRN-mediated strand exchange of telomeric DNA. Moreover, TRF2 is displaced from telomeric DNA by WRN, independent of its ATPase and helicase activities. Together, these results suggest that TRF2 and WRN act coordinately during telomeric recombination processes, consistent with certain telomeric abnormalities associated with alteration of WRN function.
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DOI：
10.1073/pnas.1006338107
发表时间：
2010-09-07
影响因子：
11.1
作者：
Hagelstrom, R. Tanner;Blagoev, Krastan B.;Bailey, Susan M.
通讯作者：
Bailey, Susan M.
影响因子：
30.8
作者：
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deLange, T
DOI：
10.1073/pnas.0609410104
发表时间：
2007-02-13
影响因子：
11.1
作者：
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通讯作者：
Karlseder, Jan
影响因子：
5.3
作者：
Goto, M
通讯作者：
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影响因子：
11.4
作者：
Bianchi, A;Stansel, RM;de Lange, T
通讯作者：
de Lange, T