DNA repair protein RAD50; hRAD50 (RAD50)

Function

• component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity & meiosis
• within the MRN complex, RAD50 may be required to bind DNA ends & hold them in close proximity; this could facilitate searches for short or long regions of sequence homology in the recombining DNA templates, & may also stimulate activity of DNA ligases &/or restrict nuclease activity of MRE11A to prevent nucleolytic degradation past a given point
• phosphorylated upon DNA damage, probably by ATM or ATR
• component of the BASC complex
• found in a complex with TERF2
• interacts with RINT1
• interacts with BRCA1 via its N-terminal domain
• interacts with DCLRE1C/Artemis

Cofactor: binds 1 Zn+2 per homodimer (putative)

Structure

• the Zn+2-hook, which separates the large intramolecular coiled coil regions, contains 2 Cys that coordinate one molecule of Zn+2 with the help of the 2 Cys of the Zn+2-hook of another RAD50 molecule, thereby forming a V-shaped homodimer
• the two heads of the homodimer, which constitute the ATP-binding domain, interact with the MRE11A homodimer
• belongs to the SMC family, RAD50 subfamily
• contains 1 Zn+2-hook domain

Compartment

• nucleus, telomere
• localizes to discrete nuclear foci after treatment with genotoxic agents

Alternative splicing

named isoforms=3

Expression

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

More general terms

• DNA-binding protein
• zinc finger protein
• phosphoprotein

Component of

• BRCA1-associated genome surveillance complex (BASC)
• MRN complex

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=10111
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:10111
• OMIM: https://mirror.omim.org/entry/604040
• UniProt: http://www.uniprot.org/uniprot/Q92878.html