Uncoupling of leading- and lagging-strand DNA replication during lesion bypass in vivo.
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.
Pagès
Vincent
V
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.
Fuchs
Robert P
RP
D015073:2-Acetylaminofluorene / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism; D004249:DNA Damage; D004257:DNA Polymerase II / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D004261:DNA Replication; D004269:DNA, Bacterial / Q000096:biosynthesis*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins; D006147:Guanine / Q000378:metabolism; D007700:Kinetics; D010957:Plasmids; D013014:SOS Response, Genetics
D018736:DNA Adducts; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D006147:Guanine; D015073:2-Acetylaminofluorene; D004257:DNA Polymerase II; C120926:DNA polymerase V, E coli; D004259:DNA-Directed DNA Polymerase