Register-Shifted Structures in Base-Flipped Uracil-Damaged DNA.

We report the occurrence of register-shifted structures in simulations of uracil-containing dsDNA. These occur when the 3' base vicinal to uracil is thymine in U:A base-paired DNA. Upon base flipping of uracil, this 3' thymine hydrogen bonds with the adenine across the uracil instead of its complementary base. The register-shifted structure is persistent and sterically blocks re-entry of uracil into the helix stack. Register shifting might be important for DNA repair since the longer exposure of the lesion in register-shifted structures could facilitate enzymatic recognition and repair.