Mechanics and execution of homologous recombination – biophysics to the organism

DNA, the molecule that encodes our genetic information, is under constant attack from both external and internal factors, such as UV light from the sun and by-products of cellular metabolism. These factors damage DNA and it must be repaired correctly to prevent mutations and more complex chromosome alterations, which drive ageing, cancer and other diseases. Arguably the most severe form of DNA damage is the double strand break (DSB), in which both strands of the DNA duplex are severed. Fortunately, cells possess several DNA repair mechanisms that can rejoin or replace the genetic information at a DSB, including non-homologous end joining and homologous recombination (HR).

We will investigate the mechanics of the HR process in unprecedented detail. Much of our collaborative work will focus on the regulation of a key HR protein Rad51, which has the remarkable ability to catalyse invasion of a broken DNA molecule into an intact template DNA duplex.

Many mutations we will study are found in breast and ovarian cancers and our work will lead to an improved understanding of these diseases.