Rad50

From Wikipedia, the free encyclopedia
Jump to: navigation, search
For the computer character encoding, see RADIX-50.
RAD50 homolog (S. cerevisiae)
Identifiers
Symbols RAD50 ; NBSLD; RAD502; hRad50
External IDs OMIM604040 MGI109292 HomoloGene38092 GeneCards: RAD50 Gene
RNA expression pattern
PBB GE RAD50 208393 s at tn.png
PBB GE RAD50 209349 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 10111 19360
Ensembl ENSG00000113522 ENSMUSG00000020380
UniProt Q92878 P70388
RefSeq (mRNA) NM_005732 NM_009012
RefSeq (protein) NP_005723 NP_033038
Location (UCSC) Chr 5:
131.89 – 131.98 Mb
Chr 11:
53.65 – 53.71 Mb
PubMed search [1] [2]

DNA repair protein RAD50, also known as RAD50, is a protein that in humans is encoded by the RAD50 gene.[1]

Function[edit]

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.[1]

Structure[edit]

Rad50 is a member of the structural maintenance of chromosomes (SMC) family of proteins.[2] 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”.[3] 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.[4]

Interactions[edit]

Rad50 has been shown to interact with:

Evolutionary ancestry[edit]

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.[16] 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.[17] 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.

See also[edit]

References[edit]

  1. ^ a b "Entrez Gene: RAD50 RAD50 homolog (S. cerevisiae)". 
  2. ^ Kinoshita E, van der Linden E, Sanchez H, Wyman C (2009). "RAD50, an SMC family member with multiple roles in DNA break repair: how does ATP affect function?". Chromosome Res. 17 (2): 277–88. doi:10.1007/s10577-008-9018-6. PMID 19308707. 
  3. ^ Hopfner KP, Craig L, Moncalian G, Zinkel RA, Usui T, Owen BA, Karcher A, Henderson B, Bodmer JL, McMurray CT, Carney JP, Petrini JH, Tainer JA (August 2002). "The Rad50 zinc-hook is a structure joining Mre11 complexes in DNA recombination and repair". Nature 418 (6897): 562–6. doi:10.1038/nature00922. PMID 12152085. 
  4. ^ Moreno-Herrero F, de Jager M, Dekker NH, Kanaar R, Wyman C, Dekker C (September 2005). "Mesoscale conformational changes in the DNA-repair complex Rad50/Mre11/Nbs1 upon binding DNA". Nature 437 (7057): 440–3. doi:10.1038/nature03927. PMID 16163361. 
  5. ^ a b c Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J (2000). "BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures". Genes Dev. 14 (8): 927–39. PMC 316544. PMID 10783165. 
  6. ^ a b Chiba N, Parvin JD (2001). "Redistribution of BRCA1 among four different protein complexes following replication blockage". J. Biol. Chem. 276 (42): 38549–54. doi:10.1074/jbc.M105227200. PMID 11504724. 
  7. ^ Zhong Q, Chen CF, Li S, Chen Y, Wang CC, Xiao J, Chen PL, Sharp ZD, Lee WH (1999). "Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response". Science 285 (5428): 747–50. doi:10.1126/science.285.5428.747. PMID 10426999. 
  8. ^ Dolganov GM, Maser RS, Novikov A, Tosto L, Chong S, Bressan DA, Petrini JH (1996). "Human Rad50 is physically associated with human Mre11: identification of a conserved multiprotein complex implicated in recombinational DNA repair". Mol. Cell. Biol. 16 (9): 4832–41. PMC 231485. PMID 8756642. 
  9. ^ a b Trujillo KM, Yuan SS, Lee EY, Sung P (1998). "Nuclease activities in a complex of human recombination and DNA repair factors Rad50, Mre11, and p95". J. Biol. Chem. 273 (34): 21447–50. doi:10.1074/jbc.273.34.21447. PMID 9705271. 
  10. ^ Goedecke W, Eijpe M, Offenberg HH, van Aalderen M, Heyting C (1999). "Mre11 and Ku70 interact in somatic cells, but are differentially expressed in early meiosis". Nat. Genet. 23 (2): 194–8. doi:10.1038/13821. PMID 10508516. 
  11. ^ Cerosaletti KM, Concannon P (2003). "Nibrin forkhead-associated domain and breast cancer C-terminal domain are both required for nuclear focus formation and phosphorylation". J. Biol. Chem. 278 (24): 21944–51. doi:10.1074/jbc.M211689200. PMID 12679336. 
  12. ^ Desai-Mehta A, Cerosaletti KM, Concannon P (2001). "Distinct functional domains of nibrin mediate Mre11 binding, focus formation, and nuclear localization". Mol. Cell. Biol. 21 (6): 2184–91. doi:10.1128/MCB.21.6.2184-2191.2001. PMC 86852. PMID 11238951. 
  13. ^ Xiao J, Liu CC, Chen PL, Lee WH (2001). "RINT-1, a novel Rad50-interacting protein, participates in radiation-induced G(2)/M checkpoint control". J. Biol. Chem. 276 (9): 6105–11. doi:10.1074/jbc.M008893200. PMID 11096100. 
  14. ^ a b O'Connor MS, Safari A, Liu D, Qin J, Songyang Z (2004). "The human Rap1 protein complex and modulation of telomere length". J. Biol. Chem. 279 (27): 28585–91. doi:10.1074/jbc.M312913200. PMID 15100233. 
  15. ^ Zhu XD, Küster B, Mann M, Petrini JH, de Lange T (2000). "Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres". Nat. Genet. 25 (3): 347–52. doi:10.1038/77139. PMID 10888888. 
  16. ^ White MF (January 2011). "Homologous recombination in the archaea: the means justify the ends". Biochem. Soc. Trans. 39 (1): 15–9. doi:10.1042/BST0390015. PMID 21265740. 
  17. ^ Quaiser A, Constantinesco F, White MF, Forterre P, Elie C (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. 9: 25. doi:10.1186/1471-2199-9-25. PMC 2288612. PMID 18294364. 

Further reading[edit]

External links[edit]