Fork-Like DNA Templates Support Bypass Replication of Lesions that Block DNA Synthesis on Single-Stranded Templates

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 93; no. 24; pp. 13766 - 13769
• Main Authors: Hoffmann, Jean-Sebastien, Pillaire, Marie-Jeanne, Lesca, Claire, Burnouf, Dominique, Robert P. P. Fuchs, Defais, Martine, Villani, Giuseppe
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 26.11.1996; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences of the USA
• Subjects: 2-Acetylaminofluorene; Adducts; Animals; Antineoplastic Agents; Base Sequence; Biochemistry; Biological Sciences; Carcinogens; Cell extracts; CHO Cells; Cisplatin; Cricetinae; Deoxyribonucleic acid; DNA; DNA Adducts; DNA Damage; DNA Replication; DNA, Single-Stranded - chemistry; DNA, Single-Stranded - isolation & purification; DNA, Single-Stranded - metabolism; Genetics; Lesions; Molecular Sequence Data; Nucleic Acid Conformation; Oligonucleotides; Platinum; Templates, Genetic
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.93.24.13766

DNA replication is an asymmetric process involving concurrent DNA synthesis on leading and lagging strands. Leading strand synthesis proceeds concomitantly with fork opening, whereas synthesis of the lagging strand essentially takes place on a single-stranded template. The effect of this duality on DNA damage processing by the cellular replication machinery was tested using eukaryotic cell extracts and model DNA substrates containing site-specific DNA adducts formed by the anticancer drug cisplatin or by the carcinogen N-2-acetylaminofluorene. Bypass of both lesions was observed only with fork-like substrates, whereas complete inhibition of DNA synthesis occurred on damaged single-stranded DNA substrates. These results suggest a role for additional accessory factors that permit DNA polymerases to bypass lesions when present in fork-like DNA.