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The stalling of transcription at abasic sites is highly mutagenic
Sung-Lim Yu1, Sung-Keun Lee, Robert E Johnson
1Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston 77555-1061, USA.
Abstract:
Abasic (AP) sites represent one of the most frequently formed lesions in DNA. Here, we examine the consequences of the stalling of RNA polymerase II at AP sites in DNA in Saccharomyces cerevisiae. A severe inhibition of transcription occurs in strains that are defective in the removal of AP sites and that also lack the RAD26 gene, a homolog of the human Cockayne syndrome group B (CSB) gene, and, importantly, a dramatic rise in mutagenesis is incurred in such strains. From the various observations presented here, we infer that the stalling of transcription at AP sites is highly mutagenic.
Insights
DNA abasic (AP) sites stall transcription, leading to severe inhibition and increased mutagenesis in yeast lacking DNA repair genes like RAD26. Stalled transcription at AP sites is highly mutagenic.
Area of Science:
- Molecular Biology
- Genetics
- DNA Repair
Background:
- Abasic (AP) sites are common DNA lesions.
- Transcription by RNA polymerase II can stall at DNA lesions.
Purpose of the Study:
- To investigate the consequences of RNA polymerase II stalling at AP sites in Saccharomyces cerevisiae.
- To determine the mutagenic potential of transcription-stalling AP sites.
Main Methods:
- Analysis of transcription inhibition in yeast strains with defects in AP site removal and RAD26.
- Assessment of mutagenesis rates in these strains.
Main Results:
- Defects in AP site removal combined with RAD26 deficiency led to severe transcription inhibition.
- These conditions also resulted in a significant increase in mutagenesis.
Conclusions:
- Stalling of RNA polymerase II at AP sites is a major source of mutations.
- Efficient DNA repair is crucial to prevent transcription-associated mutagenesis at AP sites.