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Nucleic Acids Research Advance Access originally published online on October 28, 2006
Nucleic Acids Research 2006 34(20):6044-6050; doi:10.1093/nar/gkl757
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Nucleic Acids Research, 2006, Vol. 34, No. 20 6044-6050
© 2006 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

Replication fork regression in repetitive DNAs

Nicole Fouché, Sezgin Özgür, Debasmita Roy and Jack D. Griffith*

Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, The University of North Carolina Chapel Hill, NC 27599, USA

*To whom correspondence should be addressed. Tel: +1 919 966 2151; Fax: +1 919 966 3015; Email: jdg{at}med.unc.edu

Received July 25, 2006. Revised September 18, 2006. Accepted September 27, 2006.

Among several different types of repetitive sequences found in the human genome, this study has examined the telomeric repeat, necessary for the protection of chromosome termini, and the disease-associated triplet repeat (CTG)·(CAG)n. Evidence suggests that replication of both types of repeats is problematic and that a contributing factor is the repetitive nature of the DNA itself. Here we have used electron microscopy to investigate DNA structures formed at replication forks on large model DNAs containing these repeat sequences, in an attempt to elucidate the contributory effect that these repetitive DNAs may have on their replication. Visualization of the DNA revealed that there is a high propensity for a paused replication fork to spontaneously regress when moving through repetitive DNAs, and that this results in a four-way chickenfoot intermediate that could present a significant block to replication in vivo, possibly leading to unwanted recombination events, amplifications or deletions.


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