CGG repeats associated with DNA instability and chromosome fragility form structures that block DNA synthesis in vitro (original) (raw)
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Section on Genomic Structure and Function, National Institute of Diabetes and Kidney Diseases, National Institutes of Health
Bethesda, MD 20892–0830, USA
* To whom correspondence should be addressed
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Section on Genomic Structure and Function, National Institute of Diabetes and Kidney Diseases, National Institutes of Health
Bethesda, MD 20892–0830, USA
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Revision received:
06 September 1995
Accepted:
06 September 1995
Published:
25 October 1995
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K. Usdin, K. J. Woodford, CGG repeats associated with DNA instability and chromosome fragility form structures that block DNA synthesis in vitro, Nucleic Acids Research, Volume 23, Issue 20, 25 October 1995, Pages 4202–4209, https://doi.org/10.1093/nar/23.20.4202
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Abstract
A large increase in the length of a CGG tandem array is associated with a number of triplet expansion diseases, including fragile X syndrome, the most common cause of heritable mental retardation in humans. Expansion results in the appearance of a fragile site on the X chromosome in the region of the CGG array. We show here that CGG repeats readily form a series of barriers to DNA synthesis in vitro . These barriers form only when the (CGG) n strand is used as the template, are K + -dependent, template concentration-independent, and involve hydrogen bonding between guanines. Chemical modification experiments suggest these blocks to DNA synthesis result from the formation of a series of intrastrand tetraplexes. A number of lines of evidence suggest that both triplet expansion and chromosome fragility are the result of replication defects. Our data are discussed in the light of such evidence.
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