RAD50是抑癌基因，编码蛋白是MRE11/RAD50/NBS1 (MRN)复合物的一种亚基。MRN复合物作为DNA损伤反应（DDR）的一部分被募集到DNA双链断裂（DSB）位点处，并通过同源重组（HR）或非同源末端-连接（NHEJ）通路中进行损伤修复中其关键作用。在该复合物中，RAD50作为具有ATPase活性的灵活和动态二聚体。已有研究证明，RAD50通过维持多个RAD50分子对DNA的桥接和随后的MRN复合体对受损染色质的募集来维持基因组完整性。RAD50还具有直接通过NHEJ桥链接DNA末端的功能。RAD50突变预计导致功能丧失进而导致DNA损伤诱导MRN复合物形成的能力降低。RAD50胚系突变与Nijmegen破裂综合征的发生有关，该综合征的特征在于进行性小头畸形，身材矮小和癌症风险增加。RAD50的胚系突变增加了肿瘤易感性，类似于其他DNA修复酶的突变；并且已经在几种人类癌症中鉴定出RAD50体细胞突变。

RAD50 is a subunit of the MRE11/RAD50/NBS1 (MRN) complex. The MRN complex is recruited to the site of DNA double-strand breaks (DSBs) as part of the DNA damage response (DDR) and plays a pivotal role in the repair of damage via either the homologous recombination (HR) or non-homologous end-joining (NHEJ) pathways. Within this complex, RAD50 functions as a flexible and dynamic dimer with ATPase activity. Biochemical studies have demonstrated that RAD50 functions in the maintenance of genomic integrity via the bridging of multiple RAD50 molecules to DNA and subsequent recruitment of the MRN complex to damaged chromatin. RAD50 also has a direct function in bridging the ends of DNA that are to be repaired via NHEJ. Germline mutations in RAD50 have been identified in patients with Nijmegen breakage syndrome-like disorder, characterized by progressive microcephaly, short stature and increased risk of cancer. Mutations in RAD50 increase tumor susceptibility, similar to mutations in other DNA repair enzymes, and RAD50 somatic mutations have been identified in several human cancers. RAD50 mutations are predicted to be loss-of-function leading to the reduced ability for DNA damage-induced MRN foci to form.

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