Repair of O6-methylguanine adducts in human telomeric G-quadruplex DNA by O6-alkylguanine-DNA alkyltransferase.
Bottom Line: Its functions with short single-stranded and duplex substrates have been characterized, but its ability to act on other DNA structures remains poorly understood.Here, we examine the functions of this enzyme on O(6)-methylguanine (6mG) adducts in the four-stranded structure of the human telomeric G-quadruplex.This distinction may reflect differences in the conformational dynamics of 6mG residues in G-quadruplex DNAs.
Affiliation: Department of Molecular and Cellular Biochemistry, Center for Structural Biology, University of Kentucky, Lexington, KY 40536, USA.Show MeSH
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Mentions: For G-quadruplexes annealed and repaired in buffer containing KCl, a comparison of the amplitudes of the fast and slow reaction phases with the extent of repair is informative (Figure 8A). The amplitudes of the fast phase and reaction extent after long incubation (8.8 h) vary with position within the quadruplex, with greater values at positions G1, G3, G4 and G6 (located in outer tetrads, Figure 1), and smaller values for positions G2 and G5 (inner tetrads). Repair amplitudes for the inner tetrad residue G11, both in the standard 22-mer sequence and in an elongated 25-nt version, were similar to those at the other inner positions. This pattern suggests models in which the stacking of G-quartets influences the amplitude of the fast phase of the reaction as well as the overall extent of repair.
Affiliation: Department of Molecular and Cellular Biochemistry, Center for Structural Biology, University of Kentucky, Lexington, KY 40536, USA.