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

We report the occurrence of register-shifted structuresin simulationsof uracil-containing dsDNA. These occur when the 3 & PRIME; base vicinalto uracil is thymine in U:A base-paired DNA. Upon base flipping ofuracil, this 3 & PRIME; thymine hydrogen bonds with the adenine acrossthe uracil instead of its complementary base. The register-shiftedstructure is persistent and sterically blocks re-entry of uracil intothe helix stack. Register shifting might be important for DNA repairsince the longer exposure of the lesion in register-shifted structurescould facilitate enzymatic recognition and repair.

Automated summary

We have discovered register-shifted structures in simulations of uracil-containing dsDNA. These structures occur when a thymine is present at the 3' position adjacent to uracil in U:A base-paired DNA. The register-shifted structure persists, blocking the re-entry of uracil into the helix stack and potentially influencing DNA repair processes.