CGG repeats associated with DNA instability and chromosome fragility form structures that block DNA synthesisin vitro
Open Access
- 1 January 1995
- journal article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 23 (20) , 4202-4209
- https://doi.org/10.1093/nar/23.20.4202
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.Keywords
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