Molecular & Cellular Toxicology

The Korean Society of Toxicogenomics and Toxicoproteomics (대한독성유전 단백체학회)
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RAD2 and PUF4 Regulate Nucleotide Metabolism Related Genes, HPT1 and URA3

  • Yu, Sung-Lim (Research and Education for Functions of Biological Molecules by BK-21 Project, Department of Biological Sciences, Inha University) ;
  • Lim, Hyun-Sook (Department of Pharmacology, Inha Research Institute for Medical Sciences) ;
  • Kang, Mi-Sun (Department of Pharmacology, Inha Research Institute for Medical Sciences) ;
  • Kim, Mai Huynh (Ilsong Institute of Life Science, Hallym University) ;
  • Kang, Dong-Chul (Ilsong Institute of Life Science, Hallym University) ;
  • Lee, Sung-Keun (Department of Pharmacology, Inha Research Institute for Medical Sciences)
  • Published : 2008.12.31
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Abstract

Yeast RAD2, a yeast homolog of human XPG gene, is an essential element of nucleotide excision repair (NER), and its deletion confers UV sensitivity and NER deficiency. 6-Azauracil (6AU) sensitivity of certain rad2 mutants revealed that RAD2 has transcription elongation function. However, the fundamental mechanism by which the rad2 mutations confer 6AU sensitivity was not clearly elucidated yet. Using an insertional mutagenesis, PUF4 gene encoding a yeast pumilio protein was identified as a deletion suppressor of rad2${\Delta}$ 6AU sensitivity. Microarray analysis followed by confirmatory RT-qPCR disclosed that RAD2 and PUF4 regulated expression of HPT1 and URA3. Overexpression of HPT1 and URA3 rescued the 6AU sensitivity of rad2${\Delta}$ and puf4${\Delta}$ mutants. These results indicate that 6AU sensitivity of rad2 mutants is in part ascribed to impaired expression regulation of genes in the nucleotide metabolism. Based on the results, the possible connection between impaired transcription elongation function of RAD2/XPG and Cockayne syndrome via PUF4 is discussed.

Keywords

References

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