RecombInsight: Discovery in Mammalian Homologous Recombination DNA Repair

同源重组DNA修复（Homologous Recombination DNA repair， HR）是最精确的双链DNA断裂修复形式。促进衰老的几个基因突变与人类综合症有关，包括早发性衰老和癌症易感性。靶向HR缺乏是几种抗癌治疗的核心，而诱导有毒HR中间体是一种新兴治疗策略的基础。人力资源有两个阶段。第一种方法是修剪一条断裂的DNA链，这已经很好理解了。然而，接下来的步骤是机制上的知识差距，阻碍了对癌症易感性综合征和新疗法发展的理解。该项目旨在发现哺乳动物细胞中较少研究的HR第二阶段的分子细节。为了实现这一目标，它将确定支持这一过程的新细胞因子，并开发新的方法来评估每一步中发生的核酸和蛋白质事件。该项目将利用化学概念、改进的基因组编辑、创新的染色体构象和成像技术来实现这一转变。

Homologous Recombination DNA repair (HR) is the most accurate form of double-strand DNA break repair. Mutations in several genes that promote it are associated with human syndromes, including early-onset ageing and cancer predisposition. Targeting HR deficiency is at the core of several anti-cancer treatments while inducing toxic HR intermediates underpins an emerging therapeutic strategy. HR happens in two phases. The first involves trimming one of the broken DNA strands and is well understood. However, the next steps are mechanistic knowledge gaps, holding back understanding of cancer predisposition syndromes and new therapy developments.This project aims to discover the molecular details of this less-studied second phase of HR in mammalian cells. To achieve this it will identify new cellular factors that support the process and develop new means to assess the nucleic acid and protein events that occur at each step. The project will exploit concepts from chemistry, improved genome editing, innovative chromosome conformation and imaging technologies to deliver this step-change.