Differential replication of a single N-2-acetylaminofluorene lesion in the leading or lagging strand DNA in a human cell extract.

The Journal of Biological Chemistry
X Veaute, A R Sarasin

Abstract

DNA replication in eucaryotic cells is a complex process involving a variety of proteins that synthesize the leading and lagging strand in an asymmetric, coordinated manner. To investigate the effect of this asymmetry on the translesion synthesis of bulky lesions, we have constructed SV40 origin-containing plasmids with site-specific N-2-acetylaminofluorene adduct on either leading or lagging strand templates. These plasmids have been incubated with DNA replication-competent extracts made from human HeLa cells. Two-dimensional agarose gel electrophoresis analyses reveal a strong blockage of fork progression only when the N-2-acetylaminofluorene adduct is located on the leading strand template. Morever, the analysis revealed that replication with HeLa cell extracts of SV40 origin-dependent plasmids functions in both directions from the origin with equal efficiency but, probably due to an important asynchrony at the formation of the two forks, proceeds unidirectionally for a large number of individual molecules. The validity of the in vitro replication approach to study the fidelity of both leading- and lagging strand synthesis is discussed with regard to these new data.

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Citations

Nov 11, 1999·Mutation Research·A M Cordonnier, R P Fuchs
Aug 19, 2007·Nucleic Acids Research·Shuren LiaoHong Yan
Apr 16, 2003·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Kumiko HiguchiHisaji Maki
Nov 18, 2003·Annual Review of Genetics·Justin Courcelle, Philip C Hanawalt
Apr 26, 2007·The Journal of Biological Chemistry·Marta Fierro-FernándezJorge B Schvartzman
Apr 5, 2000·The Journal of Biological Chemistry·X ChenM F Goodman
Jul 18, 2006·Chemical Research in Toxicology·Dana C UptonSteven A Akman

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