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

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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1996-11, Vol.93 (24), p.13766-13769
Main Authors: Hoffmann, Jean-Sebastien, Pillaire, Marie-Jeanne, Lesca, Claire, Burnouf, Dominique, Robert P. P. Fuchs, Defais, Martine, Villani, Giuseppe
Format: Article
Language:English
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
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.93.24.13766