Matching DNA three bases at a time: The exchange of genetic information between DNA strands is vital for accurate DNA repair and effective meiotic cell division. Using single-molecule methods and molecular dynamics simulations, Lee et al. show that members of the family of recombinase enzymes responsible for these strand exchange reactions search for and recognize matching DNA strands three bases at a time. A single mismatch abolishes triplet recognition, except for the meiosis-specific recombinase. This enzyme can stabilize a partially mismatched triplet, reflecting the partial homology of the DNA substrates in meiosis. Science , this issue p. 977

Mutations in the BRCA1 and BRCA2 genes predispose afflicted individuals to breast, ovarian, and other cancers. The BRCA-encoded products form complexes with other tumor suppressor proteins and with the recombinase enzyme RAD51 to mediate chromosome damage repair by homologous recombination and also to protect stressed DNA replication forks against spurious nucleolytic attrition. Understanding how the BRCA tumor suppressor network executes its biological functions would provide the foundation for developing targeted cancer therapeutics, but progress in this area has been greatly hampered by the challenge of obtaining purified BRCA complexes for mechanistic studies. In this article, we review how recent effort begins to overcome this technical challenge, leading to functional and structural insights into the biochemical attributes of these complexes and the multifaceted roles that they fulfill in genome maintenance. We also highlight the major mechanistic questions that remain.