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RAD17  -  Rad17p

Saccharomyces cerevisiae S288c

Synonyms: DNA damage checkpoint control protein RAD17, DNA repair exonuclease RAD17, YOR368W
 
 
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High impact information on RAD17

  • Saccharomyces cells suffering a single unrepairable double-strand break (DSB) exhibit a long, but transient arrest at G2/M. hdf1 cells, lacking Ku70p, fail to escape from this RAD9/RAD17-dependent checkpoint [1].
  • Rad17 and Rad24 proteins may contribute directly to formation of an arrest signal by association with single-strand DNA in mitosis and meiosis [2].
  • Here, we show that after a replication perturbation, cells exhibit a mutator phenotype, which can be significantly affected by mutations in the checkpoint elements Cds1 and Rad17 or translesion synthesis polymerases DinB and Polzeta [3].
  • Here, we report the identification of human and mouse homologs of the Schizosaccharomyces pombe DNA damage checkpoint control gene rad1(+) and its Saccharomyces cerevisiae homolog RAD17 [4].
  • In addition to functioning in DNA repair checkpoints, S. cerevisiae RAD17 plays a role during meiosis to prevent progress through prophase I when recombination is interrupted [4].
 

Biological context of RAD17

 

Associations of RAD17 with chemical compounds

  • Although RAD17, RAD24 and MEC3 are not required for cell cycle arrest when S phase is inhibited by hydroxyurea (HU), they do contribute to the viability of yeast cells grown in the presence of HU, possibly because they are required for the repair of HU-induced DNA damage [9].
  • AtRAD17 mutants show increased sensitivity to the DNA-damaging chemicals bleomycin and mitomycin C (MMC), which can be reversed by complementation, suggesting that the loss of function of Rad17 disturbs DNA repair in plant cells [10].
 

Physical interactions of RAD17

  • In G(1) cells expressing the mutation, the signaling cannot proceed any further along the pathway, indicating that the Rad17 complex acts after the activation of Mec1, possibly recruiting targets for the kinase [11].
  • A dominant-negative MEC3 mutant uncovers new functions for the Rad17 complex and Tel1 [11].
 

Other interactions of RAD17

  • We demonstrate that Ddc1p interacts physically in vivo with Mec3p, and this interaction requires Rad17p [12].
  • Previously, we showed in budding yeast that RAD9 and RAD17 are checkpoint genes required for arrest in the G2 phase after DNA damage [13].
  • Expression of middle sporulation genes, as well as entry into the meiotic divisions, was restored to a dmc1 strain by mutation of RAD17 [14].
  • In contrast, middle sporulation genes were not expressed in a dmc1 strain, which fails to enter the meiotic divisions because a defect in meiotic recombination leads to a RAD17-dependent checkpoint arrest [14].
  • We have cloned the RAD17 gene by complementation of the UV sensitivity of a rad17-1 mutant and identified an ORF of 1.2 kb encoding a predicted gene product of 45.4 kDa with homology to the Schizosaccharomyces pombe rad1+ gene product and to Ustilago maydis Rec1, a known 3'->5'exonuclease [15].

References

  1. 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]
  2. A meiotic recombination checkpoint controlled by mitotic checkpoint genes. Lydall, D., Nikolsky, Y., Bishop, D.K., Weinert, T. Nature (1996) [Pubmed]
  3. Checkpoint activation regulates mutagenic translesion synthesis. Kai, M., Wang, T.S. Genes Dev. (2003) [Pubmed]
  4. Human and mouse homologs of Schizosaccharomyces pombe rad1(+) and Saccharomyces cerevisiae RAD17: linkage to checkpoint control and mammalian meiosis. Freire, R., Murguía, J.R., Tarsounas, M., Lowndes, N.F., Moens, P.B., Jackson, S.P. Genes Dev. (1998) [Pubmed]
  5. The mitotic DNA damage checkpoint proteins Rad17 and Rad24 are required for repair of double-strand breaks during meiosis in yeast. Shinohara, M., Sakai, K., Ogawa, T., Shinohara, A. Genetics (2003) [Pubmed]
  6. RAD9, RAD17, and RAD24 are required for S phase regulation in Saccharomyces cerevisiae in response to DNA damage. Paulovich, A.G., Margulies, R.U., Garvik, B.M., Hartwell, L.H. Genetics (1997) [Pubmed]
  7. Role of a complex containing Rad17, Mec3, and Ddc1 in the yeast DNA damage checkpoint pathway. Kondo, T., Matsumoto, K., Sugimoto, K. Mol. Cell. Biol. (1999) [Pubmed]
  8. Checkpoint proteins influence telomeric silencing and length maintenance in budding yeast. Longhese, M.P., Paciotti, V., Neecke, H., Lucchini, G. Genetics (2000) [Pubmed]
  9. G2/M checkpoint genes of Saccharomyces cerevisiae: further evidence for roles in DNA replication and/or repair. Lydall, D., Weinert, T. Mol. Gen. Genet. (1997) [Pubmed]
  10. The Rad17 homologue of Arabidopsis is involved in the regulation of DNA damage repair and homologous recombination. Heitzeberg, F., Chen, I.P., Hartung, F., Orel, N., Angelis, K.J., Puchta, H. Plant J. (2004) [Pubmed]
  11. A dominant-negative MEC3 mutant uncovers new functions for the Rad17 complex and Tel1. Giannattasio, M., Sommariva, E., Vercillo, R., Lippi-Boncambi, F., Liberi, G., Foiani, M., Plevani, P., Muzi-Falconi, M. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  12. Mec1p is essential for phosphorylation of the yeast DNA damage checkpoint protein Ddc1p, which physically interacts with Mec3p. Paciotti, V., Lucchini, G., Plevani, P., Longhese, M.P. EMBO J. (1998) [Pubmed]
  13. Mitotic checkpoint genes in budding yeast and the dependence of mitosis on DNA replication and repair. Weinert, T.A., Kiser, G.L., Hartwell, L.H. Genes Dev. (1994) [Pubmed]
  14. NDT80 and the meiotic recombination checkpoint regulate expression of middle sporulation-specific genes in Saccharomyces cerevisiae. Hepworth, S.R., Friesen, H., Segall, J. Mol. Cell. Biol. (1998) [Pubmed]
  15. Cloning and characterization of RAD17, a gene controlling cell cycle responses to DNA damage in Saccharomyces cerevisiae. Siede, W., Nusspaumer, G., Portillo, V., Rodriguez, R., Friedberg, E.C. Nucleic Acids Res. (1996) [Pubmed]
 
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