A topological mechanism for TRF2-enhanced strand invasion
A topological mechanism for TRF2-enhanced strand invasion
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DOI：
10.1038/nsmb1192
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发表时间：
2007-02-01
影响因子：
16.8
通讯作者：
Giraud-Panis, Marie-Josephe
中科院分区：
文献类型：
--
作者：
Amiard, Simon;Doudeau, Michel;Giraud-Panis, Marie-Josephe
端粒可以折叠成t环，这可能是由于3 '突出端侵入双链体DNA所致。端粒蛋白TRF2在体外促进了它们的形成，但关于所涉及的机制知之甚少。在这里，我们揭示了TRF2产生正超螺旋和浓缩DNA。使用各种TRF2突变体，我们证明了这种拓扑活性和刺激链入侵的能力之间的强相关性。我们还报告说，这些属性需要TRF2的TRF-homology（TRFH）域与其N-或C-末端DNA结合域的组合。我们提出，TRF2复合物，通过约束周围的DNA在自己的右手构象，可以诱导解扭的相邻的DNA，从而有利于链入侵。这种拓扑模型的影响，在t环的形成和端粒的稳态进行了讨论。
Telomeres can fold into t-loops that may result from the invasion of the 3' overhang into duplex DNA. Their formation is facilitated in vitro by the telomeric protein TRF2, but very little is known regarding the mechanisms involved. Here we reveal that TRF2 generates positive supercoiling and condenses DNA. Using a variety of TRF2 mutants, we demonstrate a strong correlation between this topological activity and the ability to stimulate strand invasion. We also report that these properties require the combination of the TRF-homology (TRFH) domain of TRF2 with either its N- or C-terminal DNA-binding domains. We propose that TRF2 complexes, by constraining DNA around themselves in a right-handed conformation, can induce untwisting of the neighboring DNA, thereby favoring strand invasion. Implications of this topological model in t-loop formation and telomere homeostasis are discussed.