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 in | Proceedings of the National Academy of Sciences - PNAS Vol. 93; no. 24; pp. 13766 - 13769 |
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Main Authors | , , , , , , |
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 |
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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. |
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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 |
AuthorAffiliation_xml | – name: 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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Notes | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 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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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 |
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