How the Presence of Minor Groove Amino Groups and Major Groove Methyl Groups on the Bases Affect DNA Base-pair Dynamics: Implications for Formation of A-tract Like Structures
In this study the base-pair opening dynamics for different RRYY steps in DNA duplexes were obtained from imino proton exchange rates measured by NMR spectroscopy. The importance of a C5-methyl group in the major groove and/or an N2-amino group in the minor groove for the dynamics was assessed by comparison of AATT, AAUU, GGCC, GGMM, IICC and IIMM steps. We show that both the N2-amino group and the C5-methyl group, separately as well as together, have a stabilizing effect on the opening dynamics. Interestingly, very similar dynamics is observed for the AATT and IIMM steps, where both steps also exhibit the extraordinary opening behaviour of the central base pair that has been associated with an A-tract type of structure (Leroy et al, 1988). Hence, presence of the C5-methyl group and absence of the N2-amino group seem to be required to form this type of structure.
Furthermore, since the monitored imino proton is located at the purine in the IM-pairs, and at the pyrimidine in the AT-pairs, the similarity in opening dynamics implies that the opening event is symmetric with regard to the two bases forming the base pair.
Leroy, J.L., Charretier, E., Kochoyan, M., and Gueron, M. (1988) Biochemistry 27, 8894-8898
Sebastian Wärmländer & Mikael Leijon
Department of Biophysics, Arrhenius Laboratories, Stockholm University,