Role of mammalian Mre11 in classical and alternative nonhomologous end joining

Open Access
Publisher Website
Google Scholar
Abstract
The MRN complex is known to have a role in the cellular response to DNA double-strand breaks in higher eukaryotes, particularly in damage signaling and checkpoint responses and homologous recombination. Now MRN is found to function in nonhomologous end joining in murine stem cells. The mammalian Mre11–Rad50–Nbs1 (MRN) complex coordinates double-strand break signaling with repair by homologous recombination and is associated with the H2A.X chromatin response to double-strand breaks, but its role in nonhomologous end joining (NHEJ) is less clear. Here we show that Mre11 promotes efficient NHEJ in both wild-type and Xrcc4−/− mouse embryonic stem cells. Depletion of Mre11 reduces the use of microhomology during NHEJ in Xrcc4+/+ cells and suppresses end resection in Xrcc4−/− cells, revealing specific roles for Mre11 in both classical and alternative NHEJ. The NHEJ function of Mre11 is independent of H2A.X. We propose a model in which both enzymatic and scaffolding functions of Mre11 cooperate to support mammalian NHEJ.