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Updated: Aug 17, 2026
Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
Published on: March 20, 2018
Transcription past DNA adducts derived from polycyclic aromatic hydrocarbons
1Department of Biology, 1009 Silver Center, 100 Washington Square East, New York University, New York, NY 10003, USA. das2@nyu.edu
Abstract:
The ability of a DNA lesion to block transcription is a function of many variables: (1) the ability of the RNA polymerase active site to accommodate the damaged base; (2) the size and shape of the adduct, which includes the specific modified base; (3) the stereochemistry of the adduct; (4) the base incorporated into the growing transcript; (5) and the local DNA sequence. Each of these parameters, either alone or in combination, can influence how a particular lesion in the genome will affect transcription elongation, resulting in potential clearance of the lesion via transcription-coupled DNA repair or in the formation of truncated or full-length transcripts that might encode defective proteins.
Insights
DNA lesions can block transcription based on RNA polymerase interaction, adduct properties, and DNA sequence. This impacts DNA repair and protein synthesis, potentially leading to defective proteins.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- DNA lesions can impede cellular processes, including transcription.
- Understanding how DNA damage affects transcription is crucial for cellular health.
Purpose of the Study:
- To elucidate the factors determining a DNA lesion's ability to block transcription.
- To explore the consequences of transcription blockage by DNA damage.
Main Methods:
- Analysis of RNA polymerase active site interactions with damaged DNA.
- Assessment of adduct size, shape, and stereochemistry.
- Evaluation of DNA sequence context and incorporated bases.
Main Results:
- Multiple factors, including active site accommodation, adduct characteristics, and DNA sequence, influence transcription blockage.
- Lesion-induced transcription stalls can trigger transcription-coupled DNA repair.
- Alternatively, truncated or full-length transcripts may be produced, potentially encoding aberrant proteins.
Conclusions:
- The impact of DNA lesions on transcription is multifactorial.
- Transcription blockage by DNA damage has significant implications for genome stability and protein function.
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