DNA Adducts from a Tumorigenic Metabolite of Benzo[ a]pyrene Block Human RNA Polymerase II Elongation in a Sequence- and Stereochemistry-dependent Manner

• Published in: Journal of molecular biology Vol. 321; no. 1; pp. 29 - 47
• Main Authors: Perlow, Rebecca A, Kolbanovskii, Alexander, Hingerty, Brian E, Geacintov, Nicholas E, Broyde, Suse, Scicchitano, David A
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 02.08.2002
• Subjects: Autoradiography; Bacteriophage T7 - enzymology; Base Sequence; Benzo(a)pyrene - chemistry; Benzo(a)pyrene - metabolism; benzo[ a]pyrene; Carcinogens - chemistry; Carcinogens - metabolism; Carcinogens - pharmacology; DNA adduct stereochemistry; DNA Adducts - chemistry; DNA Adducts - genetics; DNA Adducts - metabolism; DNA Damage; DNA Repair; DNA-Directed RNA Polymerases - chemistry; DNA-Directed RNA Polymerases - metabolism; Humans; Models, Molecular; Nucleic Acid Conformation; Promoter Regions, Genetic - genetics; Protein Conformation; RNA polymerase II; RNA Polymerase II - chemistry; RNA Polymerase II - metabolism; Stereoisomerism; Substrate Specificity; Templates, Genetic; Thermodynamics; transcription; transcription junction structure; Transcription, Genetic; Viral Proteins; (+)- ca[BP]G, (+)- cis- anti-[BP]- N 2-deoxyguanosine; transcription; DNA adduct stereochemistry; PAH, polycyclic aromatic hydrocarbon; BPDE, 7,8-dihydroxy-9,10-epoxybenzo[ a]pyrene diol epoxide; (−)- anti-BPDE, (−)-7( S),8( R),9( R),10( S) BPDE; (+)- ta[BP]G, (+)- trans- anti-[BP]- N 2 deoxyguanosine; benzo[ a]pyrene; T7RNAP, T7 RNA polymerase; NER, nucleotide excision repair; (−)- ta[BP]G, (−)- trans- anti-[BP]- N 2 deoxyguanosine; GG-NER, global genomic nucleotide excision repair; transcription junction structure; BP, benzo[ a]pyrene; CMV, cytomegalovirus; (−)- ca[BP]G, (−)- cis- anti-[BP]- N 2-deoxyguanosine; (+)- anti-BPDE, (+)-7( R),8( S),9( S),10( R) BPDE; RNAPII, RNA polymerase II; RNA polymerase II; TC-NER, transcription-coupled nucleotide excision repair

Many carcinogens exert their cancer-causing effects by reacting with DNA either directly or following metabolic activation, resulting in covalently linked combination molecules known as carcinogen-DNA adducts. The presence of such lesions in the genome increases the error frequency of the replicatio...