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RAD2  -  Rad2p

Saccharomyces cerevisiae S288c

Synonyms: DNA repair protein RAD2, YGR258C
 
 
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Disease relevance of RAD2

 

High impact information on RAD2

  • Bacteriophage T4 RNase H is a 5' to 3' exonuclease that removes RNA primers from the lagging strand of the DNA replication fork and is a member of the RAD2 family of eukaryotic and prokaryotic replication and repair nucleases [4].
  • The RAD2 gene is one of at least seven genes indispensable for excision repair in the yeast Saccharomyces cerevisiae, and its encoded protein shares remarkable homology with the XP group-G gene product [6].
  • Alignment of these three polypeptides, together with two other RAD2 related proteins, reveals that their conserved sequences are largely confined to two regions [5].
  • We show that YKL510 and a truncated RAD2 protein are also structure-specific endonucleases [7].
  • The substrate specificity of the truncated RAD2 protein implicates branched DNA structures as important intermediates in nucleotide excision repair [7].
 

Biological context of RAD2

  • We have assessed the effect of bound photolyase on the dark survival of yeast cells carrying mutations in genes that eliminate either nucleotide excision repair (RAD2) or mutagenic repair (RAD18) [8].
  • We conclude that repair of oxidative DNA damage, such as thymine glycols, can be coupled to transcription and that RAD2 facilitates transcription-coupled repair of oxidative DNA damage in yeast [9].
  • Cell-cycle progression was inhibited in excision repair-defective rad1 mutants, but not in rad2 cells, indicating a role for Rad1 processing of the DSB ends [10].
  • Complementary functions of the Saccharomyces cerevisiae Rad2 family nucleases in Okazaki fragment maturation, mutation avoidance, and chromosome stability [11].
  • Rad2 family nucleases, identified by sequence similarity within their catalytic domains, function in multiple pathways of DNA metabolism [11].
 

Anatomical context of RAD2

  • Promoter analysis determined that mouse XPG is expressed constitutively and probably initiates transcription from multiple start sites, yet, unlike the yeast homolog RAD2, we found no evidence that it is UVC inducible in cultured cells [12].
 

Associations of RAD2 with chemical compounds

 

Regulatory relationships of RAD2

  • The SPK1 upstream region also includes a domain highly homologous to sequences involved in induction of RAD2 and other excision repair genes by agents that induce DNA damage. spk1 strains were hypersensitive to UV irradiation [18].
  • We have studied the molecular nature of ade2 mutations induced by UV light and bifunctional acridine-mustard (BAM) in wild-type (RAD) and in excision-deficient (rad2) strains of the yeast, Saccharomyces cerevisiae [19].
 

Other interactions of RAD2

  • Repair synthesis in vitro was defective in extracts of rad1, rad2, and rad10 mutant cells, all of which have mutations in genes whose products are known to be required for NER in vivo [14].
  • Deletion of UME6 abolishes this induction, decreases the steady-state concentration of photolyase molecules and PHR1 mRNA, and increases the UV sensitivity of a rad2 mutant [20].
  • Characterization of a mutant strain of Saccharomyces cerevisiae with a deletion of the RAD27 gene, a structural homolog of the RAD2 nucleotide excision repair gene [21].
  • These results suggest that the pathway dependent upon the expression of RAD50-55 loci functions more efficiently in budding cells compared with the pathway dependent on RAD2 and RAD6, 9 and 18 loci [22].
  • In this report, we show that the RAD2, RAD7, and RAD10 genes are also necessary for this processing [23].
 

Analytical, diagnostic and therapeutic context of RAD2

References

  1. Requirement of yeast RAD2, a homolog of human XPG gene, for efficient RNA polymerase II transcription. implications for Cockayne syndrome. Lee, S.K., Yu, S.L., Prakash, L., Prakash, S. Cell (2002) [Pubmed]
  2. Saccharomyces cerevisiae exonuclease-1 plays a role in UV resistance that is distinct from nucleotide excision repair. Qiu, J., Guan, M.X., Bailis, A.M., Shen, B. Nucleic Acids Res. (1998) [Pubmed]
  3. Overexpression of the RAD2 gene of S. cerevisiae: identification and preliminary characterization of Rad2 protein. Nicolet, C.M., Friedberg, E.C. Yeast (1987) [Pubmed]
  4. Structure of bacteriophage T4 RNase H, a 5' to 3' RNA-DNA and DNA-DNA exonuclease with sequence similarity to the RAD2 family of eukaryotic proteins. Mueser, T.C., Nossal, N.G., Hyde, C.C. Cell (1996) [Pubmed]
  5. Complementation of the DNA repair defect in xeroderma pigmentosum group G cells by a human cDNA related to yeast RAD2. Scherly, D., Nouspikel, T., Corlet, J., Ucla, C., Bairoch, A., Clarkson, S.G. Nature (1993) [Pubmed]
  6. Yeast excision repair gene RAD2 encodes a single-stranded DNA endonuclease. Habraken, Y., Sung, P., Prakash, L., Prakash, S. Nature (1993) [Pubmed]
  7. Functional domains within FEN-1 and RAD2 define a family of structure-specific endonucleases: implications for nucleotide excision repair. Harrington, J.J., Lieber, M.R. Genes Dev. (1994) [Pubmed]
  8. Interactions between yeast photolyase and nucleotide excision repair proteins in Saccharomyces cerevisiae and Escherichia coli. Sancar, G.B., Smith, F.W. Mol. Cell. Biol. (1989) [Pubmed]
  9. The yeast RAD2, but not RAD1, gene is involved in the transcription-coupled repair of thymine glycols. Leadon, S.A., Barbee, S.L., Dunn, A.B. Mutat. Res. (1995) [Pubmed]
  10. Repair of endonuclease-induced double-strand breaks in Saccharomyces cerevisiae: essential role for genes associated with nonhomologous end-joining. Lewis, L.K., Westmoreland, J.W., Resnick, M.A. Genetics (1999) [Pubmed]
  11. Complementary functions of the Saccharomyces cerevisiae Rad2 family nucleases in Okazaki fragment maturation, mutation avoidance, and chromosome stability. Sun, X., Thrower, D., Qiu, J., Wu, P., Zheng, L., Zhou, M., Bachant, J., Wilson, D.M., Shen, B. DNA Repair (Amst.) (2003) [Pubmed]
  12. Molecular cloning and structural analysis of the functional mouse genomic XPG gene. Ludwig, D.L., Mudgett, J.S., Park, M.S., Perez-Castro, A.V., MacInnes, M.A. Mamm. Genome (1996) [Pubmed]
  13. Nucleotide excision repair genes from the yeast Saccharomyces cerevisiae. Friedberg, E.C., Fleer, R., Naumovski, L., Nicolet, C.M., Robinson, G.W., Weiss, W.A., Yang, E. Basic Life Sci. (1986) [Pubmed]
  14. Nucleotide-excision repair of DNA in cell-free extracts of the yeast Saccharomyces cerevisiae. Wang, Z., Wu, X., Friedberg, E.C. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  15. Nucleotide sequence, transcript mapping, and regulation of the RAD2 gene of Saccharomyces cerevisiae. Madura, K., Prakash, S. J. Bacteriol. (1986) [Pubmed]
  16. Regulation of the RAD2 gene of Saccharomyces cerevisiae. Siede, W., Robinson, G.W., Kalainov, D., Malley, T., Friedberg, E.C. Mol. Microbiol. (1989) [Pubmed]
  17. Role of the Schizosaccharomyces pombe F-Box DNA helicase in processing recombination intermediates. Morishita, T., Furukawa, F., Sakaguchi, C., Toda, T., Carr, A.M., Iwasaki, H., Shinagawa, H. Mol. Cell. Biol. (2005) [Pubmed]
  18. SPK1 is an essential S-phase-specific gene of Saccharomyces cerevisiae that encodes a nuclear serine/threonine/tyrosine kinase. Zheng, P., Fay, D.S., Burton, J., Xiao, H., Pinkham, J.L., Stern, D.F. Mol. Cell. Biol. (1993) [Pubmed]
  19. The rad2 mutation affects the molecular nature of UV and acridine-mustard-induced mutations in the ADE2 gene of Saccharomyces cerevisiae. Ivanov, E.L., Kovaltzova, S.V., Kassinova, G.V., Gracheva, L.M., Korolev, V.G., Zakharov, I.A. Mutat. Res. (1986) [Pubmed]
  20. Role of UME6 in transcriptional regulation of a DNA repair gene in Saccharomyces cerevisiae. Sweet, D.H., Jang, Y.K., Sancar, G.B. Mol. Cell. Biol. (1997) [Pubmed]
  21. Characterization of a mutant strain of Saccharomyces cerevisiae with a deletion of the RAD27 gene, a structural homolog of the RAD2 nucleotide excision repair gene. Reagan, M.S., Pittenger, C., Siede, W., Friedberg, E.C. J. Bacteriol. (1995) [Pubmed]
  22. Genetic control of budding-cell resistance in the diploid yeast Saccharomyces cerevisiae exposed to gamma-radiation. Rao, B.S., Reddy, N.M. Mutat. Res. (1982) [Pubmed]
  23. Interaction of excision repair gene products and mitotic recombination functions in yeast. Montelone, B.A., Liang-Chong, B.C. Curr. Genet. (1993) [Pubmed]
  24. A yeast excision-repair gene is inducible by DNA damaging agents. Robinson, G.W., Nicolet, C.M., Kalainov, D., Friedberg, E.C. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  25. Evolutionary conservation of excision repair in Schizosaccharomyces pombe: evidence for a family of sequences related to the Saccharomyces cerevisiae RAD2 gene. Carr, A.M., Sheldrick, K.S., Murray, J.M., al-Harithy, R., Watts, F.Z., Lehmann, A.R. Nucleic Acids Res. (1993) [Pubmed]
  26. Purification and characterization of the DNA polymerase alpha associated exonuclease: the RTH1 gene product. Zhu, F.X., Biswas, E.E., Biswas, S.B. Biochemistry (1997) [Pubmed]
  27. Cloning and transcriptional analysis of the ADE6 gene of Saccharomyces cerevisiae. Gianì, S., Manoni, M., Breviario, D. Gene (1991) [Pubmed]
 
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