Replication fork regression in repetitive DNAs

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Replication fork regression in repetitive DNAs

Publisher
Oxford University Press
Publication Date
Oct 28, 2006
Source
PMC
Keywords
Disciplines
  • Biology
  • Chemistry
  • Medicine
License
Unknown

Abstract

gkl757 6044..6050 Replication fork regression in repetitive DNAs Nicole Fouche´, Sezgin O¨zgu¨r, 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 Received July 25, 2006; Revised September 18, 2006; Accepted September 27, 2006 ABSTRACT 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. INTRODUCTION Repetitive DNA sequences found in the human genome consist of repeat units ranging from mono-, di- and tri- nucleotide repeats to long repeating units found in Alu and LINE elements. Overall, repetitive DNA makes up �30% of the human genome with the Alu and LINE elements constituting the greatest amount (1). The short sequence units which include the triplet and telomeric repeats are of particular interest due to the high number of repeats per unit length of DNA which may bestow unique biological and physical properties. The triplet repeats which include (CGG)n�(CCG)n, (CAG)n�(CTG)n and (GAA)n�(TTC)n have been implicated

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