RAD50
Identifiers
Aliases	RAD50, NBSLD, RAD502, hRad50, Rad50, RAD50 double strand break repair protein
External IDs	OMIM: 604040, 613078 MGI: 109292 HomoloGene: 38092 GeneCards: RAD50
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q31.1 Start 132,556,019 bp[1] End 132,646,349 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11 B1.3|11 31.98 cM Start 53,540,346 bp[2] End 53,598,146 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in corpus callosum Achilles tendon islet of Langerhans stromal cell of endometrium thymus sural nerve ganglionic eminence bone marrow cells urinary bladder muscle tissue Top expressed in secondary oocyte internal carotid artery Paneth cell ovary external carotid artery corneal stroma primitive streak white adipose tissue cumulus cell medullary collecting duct More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding protein-macromolecule adaptor activity nucleotide binding DNA helicase activity metal ion binding single-stranded DNA endodeoxyribonuclease activity ATPase activity protein binding 3'-5' exonuclease activity hydrolase activity ATP binding double-stranded telomeric DNA binding adenylate kinase activity G-quadruplex DNA binding single-stranded telomeric DNA binding Cellular component site of double-strand break membrane nucleoplasm chromosome telomere nucleus condensed nuclear chromosome Mre11 complex Biological process reciprocal meiotic recombination DNA recombination telomere maintenance via telomerase positive regulation of kinase activity telomeric 3' overhang formation cellular response to DNA damage stimulus positive regulation of telomere maintenance negative regulation of telomere capping DNA duplex unwinding meiosis double-strand break repair positive regulation of protein autophosphorylation cell cycle viral process double-strand break repair via nonhomologous end joining telomere maintenance regulation of mitotic recombination nucleic acid phosphodiester bond hydrolysis DNA replication DNA double-strand break processing telomere maintenance via recombination DNA synthesis involved in DNA repair chromosome organization involved in meiotic cell cycle regulation of signal transduction by p53 class mediator nucleotide phosphorylation DNA repair double-strand break repair via homologous recombination strand displacement telomere capping nucleoside monophosphate phosphorylation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 10111 19360 Ensembl ENSG00000113522 ENSMUSG00000020380 UniProt Q92878 P70388 RefSeq (mRNA) NM_133482 NM_005732 NM_009012 RefSeq (protein) NP_005723 n/a Location (UCSC) Chr 5: 132.56 – 132.65 Mb Chr 11: 53.54 – 53.6 Mb PubMed search [3] [4]
Wikidata
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DNA repair protein RAD50, also known as RAD50, is a protein that in humans is encoded by the RAD50 gene.^[5]

Function

The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Rad50, a protein involved in DNA double-strand break repair. This protein forms a complex with MRE11 and NBS1 (also known as Xrs2 in yeast). This MRN complex (MRX complex in yeast) binds to broken DNA ends and displays numerous enzymatic activities that are required for double-strand break repair by nonhomologous end-joining or homologous recombination. Gene knockout studies of the mouse homolog of Rad50 suggest it is essential for cell growth and viability. Two alternatively spliced transcript variants of Rad50, which encode distinct proteins, have been reported.^[5]

Structure

Rad50 is a member of the structural maintenance of chromosomes (SMC) family of proteins.^[6] Like other SMC proteins, Rad50 contains a long internal coiled-coil domain that folds back on itself, bringing the N- and C-termini together to form a globular ABC ATPase head domain. Rad50 can dimerize both through its head domain and through a zinc-binding dimerization motif at the opposite end of the coiled-coil known as the “zinc-hook”.^[7] Results from atomic force microscopy suggest that in free Mre11-Rad50-Nbs1 complexes, the zinc-hooks of a single Rad50 dimer associate to form a closed loop, while the zinc-hooks snap apart upon binding DNA, adopting a conformation that is thought to enable zinc-hook-mediated tethering of broken DNA ends.^[8]

Interactions

Rad50 has been shown to interact with:

• BRCA1,^[9][10][11]
• MRE11A,^{[9][10][12][13][14]}
• NBN,^{[9][13][15][16]}
• RINT1,^[17]
• TERF2IP,^[18] and
• TERF2.^[18][19]

Evolutionary ancestry

Rad50 protein has been mainly studied in eukaryotes. However, recent work has shown that orthologs of the Rad50 protein are also conserved in extant prokaryotic archaea where they likely function in homologous recombinational repair.^[20] In the hyperthermophilic archeon Sulfolobus acidocaldarius, the Rad50 and Mre11 proteins interact and appear to have an active role in repair of DNA damages introduced by gamma radiation.^[21] These findings suggest that eukaryotic Rad50 may be descended from an ancestral archaeal Rad50 protein that served a role in homologous recombinational repair of DNA damage.

Diseases

Human RAD50 deficiency is an autosomal recessive syndrome that has been reported in patients with microcephaly and short stature. Their clinical phenotype resembled Nijmegen Breakage Syndrome. Cells from these patients showed increased radiosensitity with an impaired response to chromosome breaks. ^[22][23][24]

See also

• MRN complex
• Homologous recombination
• Nijmegen Breakage Syndrome

References

Further reading

External links

• RAD50 human gene location in the UCSC Genome Browser.
• RAD50 human gene details in the UCSC Genome Browser.