Radiosensitivity as support for the structure of a unimolecular DNA quadruplex.

PURPOSE

To search for possible variations of radiosensitivity along a unimolecular DNA quadruplex and to use them as support for choosing one of the two possible structures proposed by NMR studies.

MATERIALS AND METHODS

The probability of radiation-induced frank strand breaks (FSB) and of alkali-revealed breaks (ARB) at each nucleotide site along the oligomer AATTCGTGGAGCACC (T4G4)4, was determined by sequencing gel electrophoresis as has been previously described in the literature. The oligomer was irradiated as a unimolecular quadruplex (QS) or paired to its complementary oligonucleotide in a double-stranded B-helix (DS).

RESULTS

The oligomer globally presents the same radiosensitivity in the quadruplex or in the double-stranded helix. FSB occur with the same probability at each nucleotide site in both QS- and DS-DNA. More ARB are induced at T- and less at G-sites in QS-DNA. The probability of ARB induction in the second T-run is lower than in the first and the third one.

CONCLUSION

Intrastrand radiosensitivity variations support the folding of the studied oligomer into a quadruplex with two lateral loops and one central loop of T-runs spanning the diagonal of the terminal G-quartet.