A molecular model for RecA-promoted strand exchange via parallel triple-stranded helices
A molecular model for RecA-promoted strand exchange via parallel triple-stranded helices
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DOI：
10.1016/s0006-3495(99)77004-9
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发表时间：
1999-09-01
影响因子：
3.4
通讯作者：
Prévost, C
中科院分区：
文献类型：
--
作者：
Bertucat, G;Lavery, R;Prévost, C
许多研究已经得出结论，RecA复合的DNA单链和同源DNA双链体之间的链交换通过双链体小沟的单链侵入发生。使用分子建模，我们先前已经证明了形成平行三螺旋的可能性，其中单链通过新的碱基相互作用与小沟中的完整双链体相互作用（Bertucat等人，J. Biomol.结构动力学16：535-546）。该三倍体通过RecA施加的拉伸和解旋而稳定。在本研究中，我们表明，该三倍体内的碱基被适当地放置进行链交换。链交换被发现是放热的，并导致在一个三重螺旋中，新的单链占据的主要沟。这种结构可以等同于所谓的R型DNA，可以通过压缩和重绕进一步稳定。因此，我们能够提出一个详细的，原子尺度的RecA促进链交换模型。这个模型得到了各种实验数据的支持，表明RecA的作用主要是为单链将来的相互作用做准备，引导对双链体DNA的小沟攻击，并稳定所得的拉伸三聚体，这本质上有利于链交换。我们还讨论了这种机制如何将同源识别。
A number of studies have concluded that strand exchange between a RecA-complexed DNA single strand and a homologous DNA duplex occurs via a single-strand invasion of the minor groove of the duplex. Using molecular modeling, we have previously demonstrated the possibility of forming a parallel triple helix in which the single strand interacts with the intact duplex in the minor groove, via novel base interactions (Bertucat et al., J. Biomol. Struct Dynam. 16:535-546). This tripler is stabilized by the stretching and unwinding imposed by RecA. In the present study, we show that the bases within this tripler are appropriately placed to undergo strand exchange. Strand exchange is found to be exothermic and to result in a triple helix in which the new single strand occupies the major groove. This structure, which can be equated to so-called R-form DNA, can be further stabilized by compression and rewinding. We are consequently able to propose a detailed, atomic-scale model of RecA-promoted strand exchange. This model, which is supported by a variety of experimental data, suggests that the role of RecA is principally to prepare the single strand for its future interactions, to guide a minor groove attack on duplex DNA, and to stabilize the resulting, stretched tripler, which intrinsically favors strand exchange. We also discuss how this mechanism can incorporate homologous recognition.