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Gene Review

DDR48  -  DNA damage-responsive protein 48

Saccharomyces cerevisiae S288c

Synonyms: DDRP 48, FSP, Flocculent-specific protein, Stress protein DDR48, YM8010.03, ...
 
 
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High impact information on DDR48

  • Although the ddr48 mutant showed a slightly altered sensitivity to killing by 4-nitroquinoline-1-oxide and to heat shock compared with the DDR48 haploid, the spontaneous mutation rate of reversion of a his4 mutation was reduced 6- to 14-fold in the ddr48 strain [1].
  • Viable haploid cells containing the DDR48 gene disruption were isolated after tetrad analysis [1].
  • DNA sequence analysis of the DDR48 gene demonstrates the presence of two overlapping open reading frames, each of which has the capacity to encode a protein with a molecular mass of approximately 45 kilodaltons [1].
  • Structure of the DNA damage-inducible gene DDR48 and evidence for its role in mutagenesis in Saccharomyces cerevisiae [1].
  • The function of the DDR48 gene was investigated by disrupting this gene in diploid cells [1].
 

Biological context of DDR48

  • Although the rad mutations influence the kinetics of transcript accumulation, these effects do not account for the altered dose responses of the DDRA2 and DDR48 genes [2].
  • The roles of the RAD genes of Saccharomyces cerevisiae in the regulation of transcription of two DNA damage responsive (DDR) genes were investigated by examining the levels of the DDRA2 and DDR48 transcripts in different rad mutants after exposure to two different DNA damaging agents [2].
  • Thus, we were unable to verify that disruption of DDR48 causes an antimutator phenotype [3].
 

Anatomical context of DDR48

  • We also instilled FYP or FSP via the trachea into rabbit lungs and after 1 day, 1 week, 1 month, and 3 months lavaged the lungs and measured the pH in AM (in vivo procedure) [4].
  • Electron microscopy showed a larger number of lysosomes in contact with phagosomes and a higher percentage of vacuolated phagosomes for FYP than for FSP [4].
  • We studied phagolysosomal pH in alveolar macrophages (AM) using fluorescein-labeled yeast (FYP) and silica particles (FSP) as probes [4].
  • The intraphagosomal pH was lower when the macrophages were allowed to phagocytize the FSP in vivo [5].
  • 8. Both 3 and 24 h after lavage, more lysosomes were in contact with the FYP-containing phagosomes than with the FSP-containing ones [5].
 

Associations of DDR48 with chemical compounds

  • The regulation of the divergent ALD2 and DDR48 genes, however, occurs by different mechanisms [6].
  • A 0.45-kilobase transcript homologous to the DDRA2 gene and a 1.25-kilobase transcript homologous to the DDR48 gene accumulated after exposure of cells to 4-nitroquinoline-1-oxide (NQO; 1 to 1.5 microgram/ml) or brief heat shock (20 min at 37 degrees C) [7].
  • DDRP 48 was found to be a negatively charged and highly hydrophilic glycoprotein [8].
  • Increased DDRP 48 abundance was observed after yeast cells carrying the wild type RAD 52 gene were exposed to either ethylmethane sulfonate or heat shock treatments [8].
 

Other interactions of DDR48

  • Two of the genes, but not their osmotic induction, were already described: the DNA damage-inducible gene DDR48 and the protease inhibitor gene PAI3 [6].
  • We identified a yeast gene encoding Flocculent Specific Protein (FSP) produced excessively in the SFL1 gene-disrupted flocculent strain [9].
  • However, disruption of DDR48 did not decrease the rates of spontaneous forward mutation in a plasmid-borne copy of the yeast SUP4-o gene, the reversion or suppression of the lys2-1 allele, or forward mutation at the CAN1 locus [3].
 

Analytical, diagnostic and therapeutic context of DDR48

  • The Western blot analysis demonstrated that DDRP 48 was expressed to various concentrations in different S. cerevisiae strains [8].
  • Three hours after lavage, pH was the same as after 24 h for the FSP but significantly higher for the FYP, 5 [5].

References

  1. Structure of the DNA damage-inducible gene DDR48 and evidence for its role in mutagenesis in Saccharomyces cerevisiae. Treger, J.M., McEntee, K. Mol. Cell. Biol. (1990) [Pubmed]
  2. Transcriptional regulation of DNA damage responsive (DDR) genes in different rad mutant strains of Saccharomyces cerevisiae. Maga, J.A., McClanahan, T.A., McEntee, K. Mol. Gen. Genet. (1986) [Pubmed]
  3. Failure to detect an antimutator phenotype following disruption of the Saccharomyces cerevisiae DDR48 gene. Roche, H., Ramachandran, K., Kunz, B.A. Curr. Genet. (1995) [Pubmed]
  4. Phagolysosomal pH in alveolar macrophages. Nyberg, K., Johansson, U., Johansson, A., Camner, P. Environ. Health Perspect. (1992) [Pubmed]
  5. Intraphagosomal pH in alveolar macrophages studied with fluorescein-labeled amorphous silica particles. Nyberg, K., Johansson, A., Camner, P. Exp. Lung Res. (1989) [Pubmed]
  6. A genomic locus in Saccharomyces cerevisiae with four genes up-regulated by osmotic stress. Miralles, V.J., Serrano, R. Mol. Microbiol. (1995) [Pubmed]
  7. DNA damage and heat shock dually regulate genes in Saccharomyces cerevisiae. McClanahan, T., McEntee, K. Mol. Cell. Biol. (1986) [Pubmed]
  8. Purification and characterization of Saccharomyces cerevisiae DNA damage-responsive protein 48 (DDRP 48). Sheng, S., Schuster, S.M. J. Biol. Chem. (1993) [Pubmed]
  9. Molecular cloning of the gene encoding a highly expressed protein in SFL1 gene-disrupted flocculating yeast. Tonouchi, A., Fujita, A., Kuhara, S. J. Biochem. (1994) [Pubmed]
 
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