Mechanisms of meiotic and mitotic recombination

 描述（由申请人提供）：纯化既是避免基因组不稳定性的手段，也是产生基因组不稳定性的过程。在减数分裂中，DNA双链断裂被修复成对于同源染色体的准确分离至关重要的交叉;在这个过程中的缺陷导致不育或非整倍体，这是妊娠丢失和三体的主要原因。相反，在有丝分裂增殖细胞中，双链断裂是一类危险的DNA损伤。在这种情况下，断裂的修复是在没有发生交叉的情况下完成的;有丝分裂细胞中交叉的形成可导致染色体重排和肿瘤发生。我实验室的研究重点是促进减数分裂细胞中交叉的机制和有丝分裂细胞中修复的非交叉结果。我们专注于解旋酶，分解重组中间体，产生非交叉和霍利迪交界分解酶，切割中间体，并可以产生交叉。我们的核心方法是利用果蝇的独特功能来解决其他模型系统难以回答的重要问题。此外，我们还开发了用于人类细胞的修复试验，进行了体外生化研究，并开始了深度测序项目。这种方法的结合将有助于继续推动复合领域的发展。

 DESCRIPTION (provided by applicant): Recombination is both a means to avoid genome instability and to a process that generates genome instability. In meiosis, DNA double-strand breaks are repaired into crossovers that are essential for accurate segregation of homologous chromosomes; defects in this process result in sterility or aneuploidy, the major cause of pregnancy loss and trisomy. Conversely, in mitotically proliferating cells double-strand breaks are a dangerous class of DNA damage. Repair of breaks in this context is done without making crossovers; formation of crossovers in mitotic cells can lead to chromosome rearrangements and tumorigenesis. Research in my laboratory focuses on mechanisms that promote crossovers in meiotic cells and non-crossover outcomes of repair in mitotic cells. We focus on helicases that disassemble recombination intermediates to generate non-crossovers and Holliday junction resolvases that cleave intermediates and can generate crossovers. Our central approach is to take advantage of unique features of Drosophila to address important questions that are difficult to answer with other model systems. In addition, we have developed repair assays to use in human cells, done in vitro biochemical studies, and begun deep sequencing projects. This combination of approaches will help to continue to drive the recombination field forward.