Replication slippage involves DNA polymerase pausing and dissociation.
Genome rearrangements can take place by a process known as replication slippage or copy-choice recombination. The slippage occurs between repeated sequences in both prokaryotes and eukaryotes, and is invoked to explain microsatellite instability, which is related to several human diseases. We analysed the molecular mechanism of slippage between short direct repeats, using in vitro replication of a single-stranded DNA template that mimics the lagging strand synthesis. We show that slippage involves DNA polymerase pausing, which must take place within the direct repeat, and that the pausing polymerase dissociates from the DNA. We also present evidence that, upon polymerase dissociation, only the terminal portion of the newly synthesized strand separates from the template and anneals to another direct repeat. Resumption of DNA replication then completes the slippage process.
Viguera
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Laboratoire de Génétique Microbienne, Institut National de la Recherche Agronomique, Domaine de Vilvert, 78350 Jouy en Josas, France. viguera@biotec.jouy.inra.fr
Canceill
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D
Ehrlich
S D
SD
D001665:Binding Sites; D004258:DNA Polymerase III / Q000378:metabolism; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D008957:Models, Genetic; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D014764:Viral Proteins / Q000378:metabolism
D014764:Viral Proteins; C069983:gene 43 protein, Enterobacteria phage T4; C034970:bacteriophage T7 induced DNA polymerase; D004258:DNA Polymerase III; D004259:DNA-Directed DNA Polymerase