Journal
NUCLEIC ACIDS RESEARCH
Volume 34, Issue 20, Pages 6044-6050Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkl757
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Funding
- NIEHS NIH HHS [R56 ES013773, ES013773, R01 ES013773] Funding Source: Medline
- NIGMS NIH HHS [GM31819, R01 GM031819] Funding Source: Medline
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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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