Double-strand break repair protein MRE11 (also named MRE11A) is an 80,6 kDa (predominant isoform) protein coded by the MRE11 gene on chromosome 11q21. Together with RAD50 and NBS1, MRE11 forms the MRN complex which is a key element in DNA damage response (DDR) and possesses both single-stranded DNA endonuclease and 3′ to 5′ exonuclease activities. The MRN complex is an early sensor for locating double strand DNA breaks (DSBs) and plays a direct role in both DSB repair and the recruiting of DDR proteins and activation of their downstream signaling. It regulates repair of DNA double-strand breaks in several contexts, including replication, telomere homeostasis, meiosis, apoptosis and immune system development. The MRN complex is involved in multiple different pathways of DSBs repair, including homologous recombination (HR), non-homologous end joining (NHEJ) and the (most error prone) pathway of microhomology-mediated end joining (MMEJ) repair. MRE11 is one of 6 enzymes required for MMEJ. MRE11 and the MRN complex are thought to play a key role in cancer radiosensitivity. MRE11 overexpressing cancers are generally considered to be more radioresistant and low-expressors are regarded as chemo-sensitive although this rule may not apply to all cancer types. Several MRE11 inhibitors are currently investigated in clinical trials as radiosensitizers.