Uncoupling of Leading- and Lagging-Strand DNA Replication During Lesion Bypass in Vivo
Abstract
Numerous agents attack DNA, forming lesions that impair normal replication. Specialized DNA polymerases transiently replace the replicative polymerase and copy past lesions, thus generating mutations, the major initiating cause of cancer. We monitored, in Escherichia coli , the kinetics of replication of both strands of DNA molecules containing a single replication block in either the leading or lagging strand. Despite a block in the leading strand, lagging-strand synthesis proceeded further, implying transient uncoupling of concurrent strand synthesis. Replication through the lesion requires specialized DNA polymerases and is achieved with similar kinetics and efficiencies in both strands.
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Primer relocation and active site misalignment can both result in primer termini with one or more correct base pairs, thereby allowing more efficient polymerization following insertion of an incorrect nucleotide or insertion opposite a lesion.
“Primer relocation and active site misalignment can both result in primer termini with one or more correct base pairs, thereby allowing more efficient polymerization following insertion of an incorrect nucleotide or insertion opposite a lesion (Refs.15, 56, 57, 59 and references therein).”
From DNA Replication Fidelity (2004) · cites this paper as [59]
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Self-citation
- Authors
- Pagès, V., & Fuchs, R. P.
- Affiliations
- Cancérogenèse et Mutagenèse Moléculaire et Structurale, Unité Propre de Recherche 9003; Centre National de la Recherche Scientifique, Ecole Supérieure de Biotechnologie Boulevard S. Brant, 67400 Strasbourg, France.
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Fuchs, Robert P.
- ORCID
- Fuchs, Robert P.
- Venue
- Science
- Published
- 2003-05-23
- Volume
- 300
- Issue
- 5623
- Pages
- 1300-1303
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2070910548
- Cited by
- 221
- References
- 20
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 7 · 2021: 9 · 2020: 4 · 2019: 4 · 2018: 11 · 2017: 8 · 2016: 7 · 2015: 4 · 2014: 15 · 2013: 10 · 2012: 11
- FWCI
- 6.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- DNA replication, lesion bypass, leading strand, lagging strand, DNA polymerase, replication block, Escherichia coli, DNA damage, mutagenesis, replication kinetics
- MeSH terms
- DNA Damage, DNA Polymerase II, DNA-Directed DNA Polymerase, DNA Repair, DNA Replication, DNA, Bacterial, Escherichia coli, Guanine, Kinetics, Plasmids, SOS Response, Genetics, 2-Acetylaminofluorene, DNA Adducts, Escherichia coli Proteins
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