Catching a (Double-Strand) Break: The Rad51 and Dmc1 Strand Exchange Proteins Can Co-occupy Both Ends of a Meiotic DNA Double-Strand Break

Broken DNA can be repaired by homologous recombination mechanisms, which initially align both ends of a DNA double-strand break (DSB) with a homologous repair template. Particularly in the context of a crowded eukaryotic nucleus, it remains mysterious how the two ends of a broken DNA molecule coordinate their actions to identify an appropriate template and initiate repair. In this issue, Brown et al. [1] provide new information that bears on how this is accomplished during meiosis. Homologous recombination is employed on a grand scale in germ cells undergoing meiosis in order to facilitate a nucleus-wide homology search that will ultimately establish links between previously unassociated homologous chromosomes [2,3]. During meiosis, homologous recombination initiates with programmed DSBs; the regulated repair of such meiotic DSBs leads to the formation of crossover recombination events between homologous chromosomes. Crossovers, in conjunction with sister chromatid cohesion, provide the attachments between homologous chromosomes that ensure their proper disjunction on the meiotic spindle. The meiotic nucleus thus provides a powerful system for investigating the molecular features and dynamics of early recombination intermediates in the context of the eukaryotic nucleus. The central task of meiosis also poses an interesting challenge to recombination machinery, as its aim is to reinforce interactions between relatively distant homologous chromatids rather than spatially proximal sister chromatids. Notably, both ends of a single broken DNAmolecule must identify the same distant repair template but behave differently with respect to one another at the site of repair; the identification of single-end invasion (SEI) meiotic recombination intermediates in budding yeast [4] suggests that the ends of meiotic DSBs engage with a homologous template in a sequential fashion, as postulated in classic doublestrand break repair (DSBR) models [5]. These challenges raise the question: How are opposite ends of a DSB controlled such that they coordinately interface with the same homologous target DNA? Among the first enzymes at the scene of a DNA break are RecA-family DNA-dependent ATPase proteins, which assemble on the 30 single-stranded DNA (ssDNA) termini associated with the DSB [6]. The resulting nucleoprotein filaments have the remarkable capacity to interrogate surrounding double-stranded DNA (dsDNA) and melt homologous duplex DNA through strand invasion and exchange events. Strand exchange involves a local reconfiguration of the DNA duplex, whereby a parental strand is displaced while the invading ssDNA filament