Keeping it real: MRX–Sae2 clipping of natural substrates

摘要

The yeast Mre11–Rad50–Xrs2 (MRX) complex and Sae2 function together to initiate DNA end resection, an essential early step in homology-dependent repair of DNA double-strand breaks (DSBs). In this issue of Genes & Development, Wang and colleagues (pp. 2331–2336) and Reginato and colleagues (pp. 2325–2330) report that a variety of physiological protein blocks, including Ku, RPA, and nucleosomes, stimulate MRX–Sae2 endonuclease cleavage in vitro. These studies have important implications for how cells deal with a range of barriers to end resection and highlight the crucial role of Sae2 in activating MRX cleavage at the correct cell cycle stage.