Double-stranded DNA break resection: from bacterial model systems to human cells

DNA breaks are highly toxic lesions, and failure to repair them correctly is associated with genomic instability leading to cell death, cancer or developmental defects. Repair of double-stranded DNA breaks by homologous recombination is initiated by resection to form a long 3(prime)-terminated ssDNA overhang. It is thought that resection is a two-step process involving structure-specific nucleases, which trim the ends in preparation for more extensive degradation by processive helicases and nucleases. Dr Dillingham is aiming to investigate how human resection factors cooperate to initiate the repair of double-stranded DNA breaks, to characterise the structure and mechanism of the minimal end resection machinery for simple DNA breaks, and to understand how the variety of nucleases involved in resection can process more complex DNA end structures such as ssDNA overhangs.