The RAD9-dependent gene trans-activation is required for excision repair of active genes but not for repair of non-transcribed DNA
Abstract
The Saccharomyces cerevisiae RAD9 and RAD24 are two cell cycle checkpoint genes required for UV-dependent up-regulation of a battery of genes involved in different metabolic pathways. RAD9 is also implicated in nucleotide excision repair (NER); however, its precise role is still unclear. For the present study, we made use of the high-resolution primer extension technique to show that the RAD9-deleted cells are deficient in the repair of both strands of the URA3 gene. Interestingly, this defect was suppressed by over-expressing the RAD24 gene, suggesting that the role of RAD9 in NER is indirect probably through the UV-dependent trans-activation of some NER factors. Accordingly, we present evidence that the inhibition of UV-related de novo protein synthesis by cycloheximide has no effect on the rad9Delta mutant while it suppresses the correcting effect of RAD24 over-expression. Importantly, we have also shown that RAD9 has no role in repair of transcriptionally inactive DNA sequences (URA3 promoter and transcriptionally silent GAL10 gene). Furthermore, de novo protein synthesis was not required for NER in the absence of transcription-coupled NER. This implies that RAD9-dependent gene up-regulation is required for NER only when this process is coupled to transcription.
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Checkpoints actively stimulate repair processes and, in higher eukaryotes, trigger apoptosis when damage cannot be successfully dealt with.
“The checkpoints also actively stimulate the repair processes [1–9] and, in higher eukaryotes, trigger the apoptotic response, if damage cannot be dealt with successfully [10–12].”
From Mind the gap: keeping UV lesions in check (2011) · cites this paper as [8]
Rad9 does not seem required for repair of non-transcribed regions, suggesting it acts only when repair is coupled to transcription.
“Rad9 does not seem to be required for the repair of non-transcribed regions, suggesting that it is acting only when repair is coupled to transcription [8].”
From Mind the gap: keeping UV lesions in check (2011) · cites this paper as [8]
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Mind the gap: keeping UV lesions in check
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“Rad9 does not seem to be equired for the repair of non-transcribed regions, suggesting that it s acting only when repair is coupled to transcription [8].”
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- Authors
- Al-Moghrabi, N. M., Al-Sharif, I. S., & Aboussekhra, A.
- Affiliations
- King Faisal Specialist Hospital & Research Centre (SA)
- Corresponding author
- Aboussekhra, Abdelilah
- Venue
- Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
- Publisher
- Elsevier BV
- Published
- 2009-04
- Volume
- 663
- Issue
- 1-2
- Pages
- 60-68
- ISSN
- 0027-5107 (ISSN-L)
- 1386-1964
- OpenAlex
- W2021458881
- Cited by
- 4
- References
- 38
- Citations by year
- 2019: 1 · 2014: 1
- FWCI
- 0.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Mutation research. Fundamental and molecular mechanisms of mutagenesis (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- Rad9, Rad24, nucleotide excision repair, GAL10, cycloheximide, de novo protein synthesis, cell cycle checkpoints, Saccharomyces cerevisiae
- MeSH terms
- Cycloheximide, DNA Repair, DNA, Fungal, Fungal Proteins, Genes, Fungal, Mutation, Promoter Regions, Genetic, Pyrimidine Dimers, Saccharomyces cerevisiae, Transcription, Genetic, Protein Biosynthesis, Ultraviolet Rays, Transcriptional Activation, Gene Expression Regulation, Fungal, Cell Cycle Proteins, Intracellular Signaling Peptides and Proteins
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