Publication highlights

BRCA2 is a tumour suppressor frequently mutated in breast and ovarian cancer. BRCA2 is a large, 3418 amino acid-long protein that plays a central role in homologous recombination, a pathway to repair broken DNA. How exactly BRCA2 acts during the repair process was unclear. To address this, researchers from the Crick and Imperial College London isolated BRCA2 and its partner, Rad51 recombinase, from cells and labelled them with fluorescent chemicals. They then used optical tweezers, powerful lasers capable of holding and moving small objects, to stretch individual single DNA molecules bearing a gap in one of the strands – mimicking DNA damage that BRCA2 and Rad51 repair in cells.

Finally, after adding labelled BRCA2 and Rad51, the researchers used fluorescence microscopy to make a movie of BRCA2 recognising and delivering Rad51 to gapped DNA in real time. The researchers analysed these movies and observed BRCA2 can recognise the DNA damage directly, bind to a border of damaged and undamaged DNA and surprisingly, also slide along DNA to reach the damaged site. When researchers engineered mutations in BRCA2, it was less able to search for DNA damage. This work shows in unprecedented detail how BRCA2 delivers Rad51 to repair DNA damage to prevent tumour formation.