title: Fork-like DNA templates support bypass replication of lesions that block DNA synthesis on single-stranded templates.
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.
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, Unité Propre de Recherche 9062, Toulouse, France.
authors.forename: J S
authors.initials: JS
authors.lastname: Hoffmann
authors.forename: M J
authors.initials: MJ
authors.lastname: Pillaire
authors.forename: C
authors.initials: C
authors.lastname: Lesca
authors.forename: D
authors.initials: D
authors.lastname: Burnouf
authors.forename: R P
authors.initials: RP
authors.lastname: Fuchs
authors.forename: M
authors.initials: M
authors.lastname: Defais
authors.forename: G
authors.initials: G
authors.lastname: Villani
mesh_terms: D015073:2-Acetylaminofluorene; D000818:Animals; D000970:Antineoplastic Agents; D001483:Base Sequence; D016466:CHO Cells; D002273:Carcinogens; D002945:Cisplatin; D006224:Cricetinae; D018736:DNA Adducts; D004249:DNA Damage; D004261:DNA Replication; D004277:DNA, Single-Stranded / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D013698:Templates, Genetic
chemical_list: D000970:Antineoplastic Agents; D002273:Carcinogens; D018736:DNA Adducts; D004277:DNA, Single-Stranded; D015073:2-Acetylaminofluorene; D002945:Cisplatin