Nucleases and helicases take center stage in homologous recombination

Homologous recombination (HR)-mediated DNA double-strand break repair maintains genome integrity. Although long-studied, an understanding of two essential steps in this process – the resection of DNA ends to produce recombinogenic 3′ single-stranded DNA tails and the resolution of recombination intermediates – has remained elusive. Recent findings show an unexpected role for the Sgs1 (BLM) helicase and Dna2 nuclease in end resection, and provide mechanistic insight into the initiation of 5′–3′ resection as well as its regulation by the cell cycle and the DNA damage response. Moreover, the identification of a novel Holliday junction resolvase, Yen1 (GEN1), and several helicases that dismantle strand invasion intermediates has increased the repertoire of nucleases and helicases capable of resolving recombination intermediates.