Rad50

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Protein-coding gene in the species Homo sapiens

title: "Rad50" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public description: "Protein-coding gene in the species Homo sapiens" topic_path: "uncategorized" source: "https://en.wikipedia.org/wiki/Rad50" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Protein-coding gene in the species Homo sapiens ::

DNA repair protein RAD50, also known as RAD50, is a protein that in humans is encoded by the RAD50 gene.

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.

Structure

Rad50 is a member of the structural maintenance of chromosomes (SMC) family of proteins. 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". 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.

Interactions

Rad50 has been shown to interact with:

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. 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. 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. In yeast, the functions controlled by the RAD50 gene are essential for normal meiosis. It appears that the normal functions specified by RAD50 are not essential for either the initial or terminal steps in meiosis, but are required for successful recombination.

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.

References

References

  1. "Entrez Gene: RAD50 RAD50 homolog (S. cerevisiae)".
  2. (2009). "RAD50, an SMC family member with multiple roles in DNA break repair: how does ATP affect function?". Chromosome Res..
  3. (August 2002). "The Rad50 zinc-hook is a structure joining Mre11 complexes in DNA recombination and repair". Nature.
  4. (September 2005). "Mesoscale conformational changes in the DNA-repair complex Rad50/Mre11/Nbs1 upon binding DNA". Nature.
  5. (1999). "Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response". Science.
  6. (2000). "BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures". Genes Dev..
  7. (2001). "Redistribution of BRCA1 among four different protein complexes following replication blockage". J. Biol. Chem..
  8. (1996). "Human Rad50 is physically associated with human Mre11: identification of a conserved multiprotein complex implicated in recombinational DNA repair". Mol. Cell. Biol..
  9. (1998). "Nuclease activities in a complex of human recombination and DNA repair factors Rad50, Mre11, and p95". J. Biol. Chem..
  10. (1999). "Mre11 and Ku70 interact in somatic cells, but are differentially expressed in early meiosis". Nat. Genet..
  11. (2001). "Distinct functional domains of nibrin mediate Mre11 binding, focus formation, and nuclear localization". Mol. Cell. Biol..
  12. (2001). "RINT-1, a novel Rad50-interacting protein, participates in radiation-induced G(2)/M checkpoint control". J. Biol. Chem..
  13. (2004). "The human Rap1 protein complex and modulation of telomere length". J. Biol. Chem..
  14. (2000). "Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres". Nat. Genet..
  15. White MF. (January 2011). "Homologous recombination in the archaea: the means justify the ends". Biochem. Soc. Trans..
  16. (2008). "The Mre11 protein interacts with both Rad50 and the HerA bipolar helicase and is recruited to DNA following gamma irradiation in the archaeon Sulfolobus acidocaldarius". BMC Mol. Biol..
  17. (January 1980). "The Role of Radiation (rad) Genes in Meiotic Recombination in Yeast". Genetics.
  18. (2009). "Human RAD50 deficiency in a Nijmegen Breakage Syndrome-like disorder". Am. J. Hum. Genet..
  19. (2020). "Human RAD50 deficiency: Confirmation of a distinctive phenotype". Am. J. Med. Genet..
  20. (2020). "A Disease-Causing Single Amino Acid Deletion in the Coiled-Coil Domain of RAD50 Impairs MRE11 Complex Functions in Yeast and Humans". Cell Rep..

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