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Nucleic Acids Res. 1995 Oct 25;23(20):4202-9.

CGG repeats associated with DNA instability and chromosome fragility form structures that block DNA synthesis in vitro.

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  • 1Section on Genomic Structure and Function, National Institute of Diabetes and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0830, USA.

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. There 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.

PMID:
7479085
[PubMed - indexed for MEDLINE]
PMCID:
PMC307363
Free PMC Article
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