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Rad50

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RAD50 homolog (S. cerevisiae)
Identifiers
Symbols RAD50; NBSLD; RAD502; hRad50
External IDs OMIM: 604040 MGI: 109292 HomoloGene: 38092 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]
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DNA repair protein RAD50, also known as RAD50, is a protein that in humans is encoded by the RAD50 gene.[1]

Contents

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.[1]

Structure

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

Rad50 has been shown to interact with RINT1,[5] MRE11A,[6][7][8][9][10] TERF2IP,[11] Nibrin,[6][9][12][13] TERF2[11][14] and BRCA1.[6][7][15]

References

  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 research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 17 (2): 277–88. 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 (2002 Aug 1). "The Rad50 zinc-hook is a structure joining Mre11 complexes in DNA recombination and repair.". Nature 418 (6897): 562–6. PMID 12152085.
  4. ^ Moreno-Herrero, F; de Jager, M; Dekker, NH; Kanaar, R; Wyman, C; Dekker, C (2005 Sep 15). "Mesoscale conformational changes in the DNA-repair complex Rad50/Mre11/Nbs1 upon binding DNA.". Nature 437 (7057): 440–3. PMID 16163361.
  5. ^ Xiao J, Liu CC, Chen PL, Lee WH (March 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.
  6. ^ a b c Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J (April 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.
  7. ^ a b Chiba N, Parvin JD (October 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.
  8. ^ Dolganov GM, Maser RS, Novikov A, Tosto L, Chong S, Bressan DA, Petrini JH (September 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 (August 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 (October 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. ^ a b O'Connor MS, Safari A, Liu D, Qin J, Songyang Z (July 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.
  12. ^ Cerosaletti KM, Concannon P (June 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.
  13. ^ Desai-Mehta A, Cerosaletti KM, Concannon P (March 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.
  14. ^ Zhu XD, Küster B, Mann M, Petrini JH, de Lange T (July 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.
  15. ^ Zhong Q, Chen CF, Li S, Chen Y, Wang CC, Xiao J, Chen PL, Sharp ZD, Lee WH (July 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.

Further reading

External links