Instability

Relation of DNA structures to instability of repeated DNA sequences

Mutations occurring at relatively low rates in genomes of all organisms may be beneficial for evolutionary purposes. They also may be harmful and cause numerous diseases. DNA structures are very important in mutagenesis: certain structures are more susceptible to mutagens than the others; complex DNA structures may also affect the normal chains of events in DNA replication and repair, as well as transcription, eventually causing small and large mutations. One class of large mutations, expansion of tri-, tetra- and pentanucleotide repeats, have received much attention during last 15 years. Most of these expansions have been associated with the development of human neurodegenerative diseases. Different models have been proposed for the expansion of repeats which presume the formation of alternative DNA structures in the repeating sequences. We have published a few papers where we studied the formation and discussed the functional significance of slipped-strand, locally unwound and triplex DNA for expansion of repeats

Publications

Oussatcheva EA, Hashem VI, Zou Y, Sinden RR, Potaman VN. (2001) Involvement of the nucleotide excision repair protein UvrA in instability of CAG•CTG repeat sequences in Escherichia coli. J. Biol. Chem. 276: 30878-30884 (link to PDF).

Sinden RR, Potaman VN, Oussatcheva EA, Pearson CE, Lyubchenko YL, Shlyakhtenko LS. (2002) Triplet repeat DNA structures and human genetic disease: dynamic mutations from dynamic DNA. J Biosci 27 (1 Suppl 1): 53-65 (link to PDF).

Potaman VN, Bissler JJ, Hashem VI, Oussatcheva EA, Lu L, Shlyakhtenko LS, Lyubchenko YL, Matsuura T, Ashizawa T, Leffak M, Benham CJ, Sinden RR. (2003) Unpaired structures in SCA10 (ATTCT)n•(AGAAT)n repeats. J. Mol. Biol. 326: 1095-1111 (request a copy).

Potaman VN, Oussatcheva EA, Lyubchenko YL, Shlyakhtenko LS, Bidichandani SI, Ashizawa T, Sinden RR. (2004) Length-dependent structure formation in Friedreich ataxia (GAA)n•(TTC)n repeats at neutral pH. Nucleic Acids Res. 32: 1224-1231 (link to PDF).