RecombInsight: Discovery in Mammalian Homologous Recombination DNA Repair

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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.