Radiosensitivity as support for the structure of a unimolecular DNA quadruplex

Abstract

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 (T G) , was determined by sequencing gel electrophoresis as 4 4 4 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 QSand 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.