Mechanism of Dmc1-mediated Meiotic Recombination in Budding Yeast

同源重组在染色体减数分离中起关键作用 减数分裂。DNA双链程序化诱导启动减数分裂重组 断裂(DSB)并涉及有丝分裂中DSB的重组修复机制 细胞。减数分裂重组受制于独特的调控过程，促进 同源染色单体之间的重组，而不是姐妹染色单体之间的重组，也调节 确保所有同源染色体的交叉型重组事件的频率 两人至少参加一次这样的活动。重组的中心步骤是同源的 链的入侵和交换。萌芽酵母和包括人类在内的许多其他生物 有一种特殊的减数分裂重组酶Dmc1，它催化减数分裂的中心步骤 重组，包括DNA序列同源性搜索，最终形成DNA 链交换形成连接重组伙伴的杂交DNA区域。一种不同的 链交换蛋白RAD51催化有丝分裂重组的中心步骤。Dmc1有 一组独特的减数分裂特异辅助蛋白，但也受有丝分裂调控 重组蛋白，包括有丝分裂重组酶RAD51。RAD51由一个 在减数分裂过程中，有丝分裂为Dmc1辅助蛋白的酶。我们小组研究的是 Dmc1促进减数分裂重组的分子机制。我们寻求 了解Dmc1的S活性是如何受到其每个辅助蛋白的调节的。这个目标是 通过结合各种先进的实验方法来实现。特别的 重要的是我们团队在生化重组过程中所做的独特努力 使用提纯的成分。为了补充我们的生化研究，我们首先开发了 研究减数分裂结构和动力学所需的工具和方法 用超分辨光学显微镜观察重组小体。我们小组还使用了分子 允许检测断裂和分支DNA重组的基因技术 中间体，以及在重组过程中发生的蛋白质-蛋白质相互作用 进程。我们试图将这些方法结合起来，以揭示 重组过程包括控制重组的监管机制。

Homologous recombination plays a critical role in reductional segregation of chromosomes in meiosis. Meiotic recombination is initiated by the programmed induction of DNA double strand breaks (DSBs) and involves a mechanism related to recombinational repair of DSBs in mitotic cells. Meiotic recombination is subject to unique regulatory processes that promote recombination between homologous chromatids rather than sister chromatids and also regulate the frequency of crossover type recombination events to ensure all homologous chromosome pairs engage in at least one such event. The central step of recombination is homologous strand invasion and exchange. Budding yeast and many other organisms including humans have a specialized meiotic recombinase, Dmc1, that catalyzes the central step of meiotic recombination which involves DNA sequence homology searching that culminates in DNA strand exchange to form regions of hybrid DNA that connect recombining partners. A different strand exchange protein, Rad51, catalyzes the central step of mitotic recombination. Dmc1 has a unique set of meiosis-specific accessory proteins, but is also regulated by mitotic recombination proteins, including the mitotic recombinase Rad51. Rad51 is converted from an enzyme in mitosis into to a Dmc1 accessory protein during meiosis. Our group studies the molecular mechanism through which Dmc1 promotes meiotic recombination. We seek to understand how Dmc1’s activity is regulated by each of its accessory proteins. This goal is achieved by combining a wide range of advanced experimental approaches. Of particular importance is our group’s unique effort to biochemically reconstitute the recombination process using purified components. To complement our biochemical studies, we were first to develop the tools and methods required to study the architecture and dynamics of meiotic recombinosomes using super-resolution light microscopy. Our group also employs molecular genetic techniques that allow detection of broken and branched DNA recombination intermediates, as well as the protein-protein interactions that occur during the recombination process. We seek to combine these approaches to uncover important mechanistic features of the recombination process including the regulatory mechanisms that control it.