Originally identified in S. cerevisiae, Rad50 is one of a group of genes, designated the Rad52 epistasis group, whose products mediate DNA double-stranded break (DSB) repair. Many of these genes, including Rad50, are conserved in humans and have a similar function to their S. cerevisiae counterparts. In yeast, a multiprotein complex of Rad50, Mre11, and XRS2 has been implicated in the nucleocytic processing of DSBs, in homologous recombination, in nonhomologous end joining, and in telomere maintenance. In humans, Rad50 and Mre11 complex with up to three additional proteins (95 kDa, 200 kDa, and 350 kDa). The 95 kDa species is thought to be human XRS2, although a separate report has identified it as Nibrin, the product of the gene mutated in Nijmegen breakage syndrome. The Rad50-Mre11-p95 complex possesses endonuclease and 3' to 5' exonuclease activity. Mre11 may provide both the endonuclease and exonuclease activity, but may also be involved in other functions related to this complex. Mre11 is ubiquitously expressed, with the highest expression in proliferating tissues. Thus, MRE11 may function in a multiprotein complex that has many roles during DNA maintenance and repair.