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Gene Review

RAD50  -  Rad50p

Saccharomyces cerevisiae S288c

Synonyms: 153 kDa protein, DNA repair protein RAD50, N0872, YNL250W
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Disease relevance of RAD50

  • Structural and functional similarities between the SbcCD proteins of Escherichia coli and the RAD50 and MRE11 (RAD32) recombination and repair proteins of yeast [1].
  • Rad50cd crystal structures identify probable protein and DNA interfaces and reveal an ABC-ATPase fold, linking Rad50 molecular mechanisms to ABC transporters, including P glycoprotein and cystic fibrosis transmembrane conductance regulator [2].
  • However, large-scale purification of the 153 kDa Rpo41 has only been reported from yeast cells, or as a recombinant from baculovirus, both sources requiring extensive purification with poor yields [3].

High impact information on RAD50


Biological context of RAD50


Anatomical context of RAD50

  • In rad50 delta cells, some DSBs are not repaired until a broken chromosome has been packaged into a spore and is subsequently germinated [10].
  • High levels of RAD50 expression was evident in the adult myocardium, a somewhat surprising observation given the absence of DNA synthesis in adult cardiomyocytes [11].

Associations of RAD50 with chemical compounds


Physical interactions of RAD50

  • Using a two-hybrid system, we found that Mre11 interacts with Rad50 and itself in vivo [16].

Co-localisations of RAD50


Regulatory relationships of RAD50

  • Physical monitoring of DNA showed that SPO13: : HO induced gene conversions both in Rad+ and in rad50 delta cells that cannot initiate normal meiotic DSBs [10].
  • These endonuclease activities of Mre11 are enhanced markedly by Rad50 but only in the presence of ATP [18].
  • Other LOH events were differentially affected in each mutant: the frequencies of all types of recombination were decreased in rad52 mutants and enhanced in rad50 mutants [19].

Other interactions of RAD50

  • Overexpression of Mre11p or Rad50p suppresses the inhibition of DSB repair by CAG(98) and significantly increases the average size of expansions found at the recipient locus [6].
  • Using a galactose-inducible HO endonuclease gene to initiate MAT switching, we have examined the effect of null mutations of RAD50 and of XRS2 on intermediate steps of this recombination event [8].
  • We have examined the interactions of rem1 mutations with rad6-1, rad50 -1, rad52-1 or spo11 -1 mutations in order to understand the basis of the rem1 hyper-rec phenotype [20].
  • Thus RAD50 and RAD51 define two separate pathways that collaborate to allow cells to survive in the absence of telomerase [9].
  • A search for highly expressed cDNAs that suppress the DNA repair deficiency of rad50 mutants yielded multiple isolates of two genes: EXO1 and TLC1 [21].

Analytical, diagnostic and therapeutic context of RAD50


  1. Structural and functional similarities between the SbcCD proteins of Escherichia coli and the RAD50 and MRE11 (RAD32) recombination and repair proteins of yeast. Sharples, G.J., Leach, D.R. Mol. Microbiol. (1995) [Pubmed]
  2. Structural biology of Rad50 ATPase: ATP-driven conformational control in DNA double-strand break repair and the ABC-ATPase superfamily. Hopfner, K.P., Karcher, A., Shin, D.S., Craig, L., Arthur, L.M., Carney, J.P., Tainer, J.A. Cell (2000) [Pubmed]
  3. Expression and purification of wild type and mutant forms of the yeast mitochondrial core RNA polymerase, Rpo41. Matsunaga, M., Jang, S.H., Jaehning, J.A. Protein Expr. Purif. (2004) [Pubmed]
  4. Saccharomyces Ku70, mre11/rad50 and RPA proteins regulate adaptation to G2/M arrest after DNA damage. Lee, S.E., Moore, J.K., Holmes, A., Umezu, K., Kolodner, R.D., Haber, J.E. Cell (1998) [Pubmed]
  5. Analysis of wild-type and rad50 mutants of yeast suggests an intimate relationship between meiotic chromosome synapsis and recombination. Alani, E., Padmore, R., Kleckner, N. Cell (1990) [Pubmed]
  6. Recombination-induced CAG trinucleotide repeat expansions in yeast involve the MRE11-RAD50-XRS2 complex. Richard, G.F., Goellner, G.M., McMurray, C.T., Haber, J.E. EMBO J. (2000) [Pubmed]
  7. Two survivor pathways that allow growth in the absence of telomerase are generated by distinct telomere recombination events. Chen, Q., Ijpma, A., Greider, C.W. Mol. Cell. Biol. (2001) [Pubmed]
  8. Mutations in XRS2 and RAD50 delay but do not prevent mating-type switching in Saccharomyces cerevisiae. Ivanov, E.L., Sugawara, N., White, C.I., Fabre, F., Haber, J.E. Mol. Cell. Biol. (1994) [Pubmed]
  9. RAD50 and RAD51 define two pathways that collaborate to maintain telomeres in the absence of telomerase. Le, S., Moore, J.K., Haber, J.E., Greider, C.W. Genetics (1999) [Pubmed]
  10. Meiotic recombination initiated by a double-strand break in rad50 delta yeast cells otherwise unable to initiate meiotic recombination. Malkova, A., Ross, L., Dawson, D., Hoekstra, M.F., Haber, J.E. Genetics (1996) [Pubmed]
  11. Mouse RAD50 has limited epitopic homology to p53 and is expressed in the adult myocardium. Kim, K.K., Daud, A.I., Wong, S.C., Pajak, L., Tsai, S.C., Wang, H., Henzel, W.J., Field, L.J. J. Biol. Chem. (1996) [Pubmed]
  12. Exo1 roles for repair of DNA double-strand breaks and meiotic crossing over in Saccharomyces cerevisiae. Tsubouchi, H., Ogawa, H. Mol. Biol. Cell (2000) [Pubmed]
  13. The yeast RAD50 gene encodes a predicted 153-kD protein containing a purine nucleotide-binding domain and two large heptad-repeat regions. Alani, E., Subbiah, S., Kleckner, N. Genetics (1989) [Pubmed]
  14. Fission yeast Rad50 stimulates sister chromatid recombination and links cohesion with repair. Hartsuiker, E., Vaessen, E., Carr, A.M., Kohli, J. EMBO J. (2001) [Pubmed]
  15. Effect of amino acid substitutions in the rad50 ATP binding domain on DNA double strand break repair in yeast. Chen, L., Trujillo, K.M., Van Komen, S., Roh, D.H., Krejci, L., Lewis, L.K., Resnick, M.A., Sung, P., Tomkinson, A.E. J. Biol. Chem. (2005) [Pubmed]
  16. Interaction of Mre11 and Rad50: two proteins required for DNA repair and meiosis-specific double-strand break formation in Saccharomyces cerevisiae. Johzuka, K., Ogawa, H. Genetics (1995) [Pubmed]
  17. Localization and dynamic relocalization of mammalian Rad52 during the cell cycle and in response to DNA damage. Liu, Y., Li, M., Lee, E.Y., Maizels, N. Curr. Biol. (1999) [Pubmed]
  18. DNA structure-specific nuclease activities in the Saccharomyces cerevisiae Rad50*Mre11 complex. Trujillo, K.M., Sung, P. J. Biol. Chem. (2001) [Pubmed]
  19. Positive and negative roles of homologous recombination in the maintenance of genome stability in Saccharomyces cerevisiae. Yoshida, J., Umezu, K., Maki, H. Genetics (2003) [Pubmed]
  20. Relationships between a hyper-rec mutation (REM1) and other recombination and repair genes in yeast. Malone, R.E., Hoekstra, M.F. Genetics (1984) [Pubmed]
  21. Differential suppression of DNA repair deficiencies of Yeast rad50, mre11 and xrs2 mutants by EXO1 and TLC1 (the RNA component of telomerase). Lewis, L.K., Karthikeyan, G., Westmoreland, J.W., Resnick, M.A. Genetics (2002) [Pubmed]
  22. Structure of the Rad50 x Mre11 DNA repair complex from Saccharomyces cerevisiae by electron microscopy. Anderson, D.E., Trujillo, K.M., Sung, P., Erickson, H.P. J. Biol. Chem. (2001) [Pubmed]
  23. Evidence for two pathways of meiotic intrachromosomal recombination in yeast. Gottlieb, S., Wagstaff, J., Esposito, R.E. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  24. Capture of extranuclear DNA at fission yeast double-strand breaks. Decottignies, A. Genetics (2005) [Pubmed]
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