Requirement of Yeast RAD2, a Homolog of Human XPG Gene, for Efficient RNA Polymerase II Transcription : Implications for Cockayne Syndrome

• Published in: Cell 2002-06, Vol.109 (7), p.823-834
• Main Authors: Lee, Sung-Keun, Yu, Sung-Lim, Prakash, Louise, Prakash, Satya
• Format: Article
• Language: English
• Subjects: Cell Cycle Proteins; Cell Division; Cockayne Syndrome - metabolism; DNA-Binding Proteins - chemistry; Endodeoxyribonucleases; Endonucleases; Fungal Proteins - chemistry; Fungal Proteins - genetics; Fungal Proteins - metabolism; Galactose - metabolism; Gene Expression Regulation, Fungal; Genes, Fungal - genetics; Humans; Mutation; Nuclear Proteins; RNA Polymerase II - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - growth & development; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Schizosaccharomyces pombe Proteins; Time Factors; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription Factors, General; Transcription, Genetic; Transcriptional Elongation Factors
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(02)00795-X

In addition to xeroderma pigmentosum, mutations in the human XPG gene cause early onset Cockayne syndrome (CS). Here, we provide evidence for the involvement of RAD2, the S. cerevisiae counterpart of XPG, in promoting efficient RNA polymerase II transcription. Inactivation of RAD26, the S. cerevisiae counterpart of the human CSB gene, also causes a deficiency in transcription, and a synergistic decline in transcription occurs in the absence of both the RAD2 and RAD26 genes. Growth is also retarded in the rad2Δ and rad26Δ single mutant strains, and a very severe growth inhibition is seen in the rad2Δ rad26Δ double mutant. From these and other observations presented here, we suggest that transcriptional defects are the underlying cause of CS.