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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Published inProceedings 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
LanguageEnglish
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
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Abstract 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.
AbstractList 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.
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.
Hoffmann et al examined the effect of the asymmetry of DNA replication on the efficiency of translesion synthesis. Results suggest a role for additional accessory factors that permit DNA polymerases to bypass lesions when present in fork-like DNA.
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. double- and single-stranded DNA replication cell extracts translesion synthesis cisplatin and N-2-acetylaminofluorene adducts
Author Robert P. P. Fuchs
Defais, Martine
Burnouf, Dominique
Villani, Giuseppe
Lesca, Claire
Hoffmann, Jean-Sebastien
Pillaire, Marie-Jeanne
AuthorAffiliation Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, Unité Propre de Recherche 9062, 205, route de Narbonne, 31 077 Toulouse, Cedex, France; and † Unité Propre de Recherche 9003 de Cancérogenèse et Mutagenèse Moléculaire et Structurale, Centre National de la Recherche Scientifique, Institut de Recherche sur le Cancer de L’Appareil Digestif, B.P. 426, 67091 Strasbourg Cedex, France
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To whom reprint requests should be addressed. e-mail: fuchs@esbs.u-strasb.fr or villani@ipbs.fr.
I. Robert Lehman, Stanford University Medical Center, Stanford, CA
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Snippet DNA replication is an asymmetric process involving concurrent DNA synthesis on leading and lagging strands. Leading strand synthesis proceeds concomitantly...
DNA replication is an asymmetric process involving concurrent DNA synthesis on leading and lagging strands. Leading strand synthesis proceeds concomitantly...
Hoffmann et al examined the effect of the asymmetry of DNA replication on the efficiency of translesion synthesis. Results suggest a role for additional...
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StartPage 13766
SubjectTerms 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
Title Fork-Like DNA Templates Support Bypass Replication of Lesions that Block DNA Synthesis on Single-Stranded Templates
URI https://www.jstor.org/stable/40975
http://www.pnas.org/content/93/24/13766.abstract
https://www.ncbi.nlm.nih.gov/pubmed/8943009
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