Abstract
Analysis of the first step in repairing double-stranded-DNA breaks reveals that the Mre11 enzyme makes a DNA nick at a point separate from the break ends, creating an entry site for further processing by exonuclease enzymes. See Letter p.122 Homologous recombination at a DNA double-strand break uses a 3′-tailed molecule, which requires resection of the 5′ strand. Previous genetic analysis indicated that the MRX complex, consisting of the repair proteins Mre11, Rad50 and Xrs2, was required for resection. However its in vitro activity was puzzling, as only 3′ to 5′ resection was detected. Elda Cannavo and Petr Cejka have now resolved this conundrum. They find that in yeast, Sae2 nuclease activates MRX to make an initial endonucleolytic cut on the 5′ strand so that MRX can digest the 5′ strand back to the end in a 3′-to-5′ fashion. This activity is stimulated by blockage of the DNA end, which is consistent with in vivo situations such as meiosis, where the Spo11 complex remains bound after initiating a double-strand break.
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