The Many Interfaces of Mre11

the television program " Saturday Night Live " touted a Usui et al., 1998; Moreau et al., 1999). These and other product that was both a dessert topping and a floor mutations (Bressan et al., 1998) are defective in DSB wax. Claims like this pile up for some notable proteins, repair after ionizing radiation. too. Assertions about p53 would give it a hand in virtually It is surprising that the Mre11 complex has in vitro every aspect of DNA and RNA metabolism. One might have similar concerns about the incredible list of jobs assigned to Mre11p, Rad50p, and p95/Xrs2p, were it not for the fact that all of them have been demonstrated in vivo. These proteins are important for two different processes of repairing of double-strand chromosome breaks, homologous recombination and nonhomolo-gous end joining, and they play a key role in telomere maintenance (Figure 1). In addition, this trio is implicated in the cell's checkpoint response to the presence of double-strand breaks (DSBs). But there's more: in meio-sis, these three proteins are required not only for the resection of DSBs, but to create the meiotic DSBs in the first place. Deletion of any of these three genes in yeast causes cells to grow slowly, and in mouse cells, the deletion of MRE11 is lethal (Xiao and Weaver, 1997). A recent flood of papers have established the basis of some of the complicated roles that Mre11, Rad50, and p95/Xrs2 proteins perform. Mre11p acts as an exo-nuclease and as an endonuclease, but has other, perhaps noncatalytic, attributes as well. In humans and in yeast, Mre11p, Rad50p, and p95 assemble into large complexes. In human cells, Trujillo et al. (1998) find complexes containing only the three proteins, but Carney et al. (1998) report the association of additional, large proteins. In yeast, Mre11p, Rad50p, and Xrs2p are associated, but in meiotic cells the complex contains two other proteins similar in size to two meiosis-specific proteins required to make DSBs in mei-osis (Usui et al., 1998 [this issue of Cell]) (Figure 1). The stoichiometry of these complexes has not been established.nuclease subunits SbcC and SbcD are homologous to myces Rad50p and Mre11p, respectively. Rad50p is a coiled-In conjunction with many different sets of proteins, the Mre11 com-coil protein with ATP-dependent DNA binding activity plex performs a surprisingly large range of functions, ranging from and shares homology with SMC proteins involved in helping the Spo11 topoisomerase …