TheMre11 Nuclease Complex

Abstract

The repair of DNA double‐strand breaks (DSBs) is necessary to maintain genome stability and prevent cell aberration and cancer development. Meiotic recombination 11 (Mre11) and radiation sensitivity 50 (Rad50) form an evolutionary conserved complex (denoted Mre11 complex) that is a key factor in the detection, repair, and signaling of DSBs. The Mre11 complex possesses ATP‐stimulated DNA binding, DNA endo‐ and exonuclease activities as well as DNA cross‐linking functions. The Mre11 complex is a primary sensor for DNA DSBs and is involved in many aspects of the repair of and cellular response to DNA DSBs. Its activity is controlled by at least three different metal binding sites, a manganese‐dependent nuclease (Mre11 phosphodiesterase domain), a magnesium‐dependent ATPase (Rad50 ABC ATPase domain), and a zinc‐mediated DNA tethering function, located at the apex of a long Rad50 coiled‐coil domain. Although the mechanism remains to be shown, current structural and functional data indicate that the Mre11 complex is an ATP‐dependent cross‐linker and a processing factor for DNA ends.