Recombinant Human DNA repair protein RAD50 (RAD50), partial

Function

Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis (PubMed:15064416, PubMed:21757780, PubMed:27889449, PubMed:28134932, PubMed:28867292, PubMed:9590181, PubMed:9651580, PubMed:9705271). The MRN complex is involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), an error-free mechanism which primarily occurs during S and G2 phases (PubMed:15064416, PubMed:21757780, PubMed:27889449, PubMed:28867292, PubMed:9590181, PubMed:9651580, PubMed:9705271). The complex (1) mediates the end resection of damaged DNA, which generates proper single-stranded DNA, a key initial steps in HR, and is (2) required for the recruitment of other repair factors and efficient activation of ATM and ATR upon DNA damage (PubMed:15064416, PubMed:27889449, PubMed:28867292, PubMed:9590181, PubMed:9651580, PubMed:9705271). The MRN complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11, to initiate end resection, which is required for single-strand invasion and recombination (PubMed:11741547, PubMed:9590181, PubMed:9651580, PubMed:9705271). Within the complex, RAD50 is both required to bind DNA ends and hold them in close proximity and regulate the activity of MRE11 (PubMed:11741547, PubMed:12805565, PubMed:28134932). RAD50 provides an ATP-dependent control of MRE11 by positioning DNA ends into the MRE11 active site: ATP-binding induces a large structural change from an open form with accessible MRE11 nuclease sites into a closed form (By similarity). The MRN complex is also required for DNA damage signaling via activation of the ATM and ATR kinases: the nuclease activity of MRE11 is not required to activate ATM and ATR (PubMed:15064416, PubMed:15790808, PubMed:16622404). The MRN complex is also required for the processing of R-loops (PubMed:31537797). In telomeres the MRN complex may modulate t-loop formation (PubMed:10888888)

Subcellular Location

Nucleus; Chromosome, telomere; Chromosome

Disease Association

Nijmegen breakage syndrome-like disorder (NBSLD) : A disorder similar to Nijmegen breakage syndrome and characterized by chromosomal instability, radiation sensitivity, microcephaly, growth retardation, short stature and bird-like face. Immunodeficiency is absent. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Expressed at very low level in most tissues, except in testis where it is expressed at higher level. Expressed in fibroblasts

Subunit

(Microbial infection) Interacts with herpes simplex virus 1 protein UL12 (PubMed:20943970)

• Dolganov G.M. et al. Human Rad50 is physically associated with human Mre11: identification of a conserved multiprotein complex implicated in recombinational DNA repair. — Mol. Cell. Biol. (1996)
• Kim K.K. et al. Molecular cloning and characterization of splice variants of human RAD50 gene. — Gene (1999)
• Offenberg H.H. et al. PubMed: CI-4P8ROG8795M6O (JUL-)
• Schmutz J. et al. The DNA sequence and comparative analysis of human chromosome 5. — Nature (2004)
• Mural R.J. et al. PubMed: CI-5GBD0VIIJ7C63 (SEP-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Carney J.P. et al. The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. — Cell (1998)
• Trujillo K.M. et al. Nuclease activities in a complex of human recombination and DNA repair factors Rad50, Mre11, and p95. — J. Biol. Chem. (1998)