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PMID: 11350948 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Replication slippage involves DNA polymerase pausing and dissociation.

The EMBO journal ·Vol. 20 ·No. 10 ·2001-05-15 ·Pages 2587-95

Viguera E, Canceill D, Ehrlich SD

Abstract

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.

MeSH Terms
Binding Sites DNA Polymerase III/metabolism DNA Replication DNA-Directed DNA Polymerase/metabolism Models, Genetic Recombination, Genetic Repetitive Sequences, Nucleic Acid Viral Proteins/metabolism
Chemicals
Viral Proteins gene 43 protein, Enterobacteria phage T4 bacteriophage T7 induced DNA polymerase DNA Polymerase III DNA-Directed DNA Polymerase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Viguera E
Laboratoire de Génétique Microbienne, Institut National de la Recherche Agronomique, Domaine de Vilvert, 78350 Jouy en Josas, France. viguera@biotec.jouy.inra.fr
Canceill D
Ehrlich S D
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/20.10.2587
Email
viguera@biotec.jouy.inra.fr
Published
2001-05-15
Pages
2587-95
Language
English
Region
England
NLM ID
8208664
PMCID
PMC125466
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/20.10.2587 PMC Full Text View journal details
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