ESSENTIAL DYNAMICS OF DNA CONTAINING A CIS.SYN CYCLOBUTANE THYMINE DIMER LESION

Conformational properties of a UV-damaged DNA decamer containing a cis .syn cyclobutane thymine dimer (PD) have been investigated by molecula r dynamics (MD) simulations. Results from MD simulations of the damage d decamer DNA show a kink of similar to 21.7 degrees at the PD damaged site and a disruption of H bonding between the 5'-thymine of the PD a nd its complementary adenine. However, no extra-helical flipping of th e 3'-adenine complementary to the PD was observed, Comparison to two u ndamaged DNA decamers, one with the same sequence and the other with a n AT replacing the TT sequence, indicates that these properties are sp ecific to the damaged DNA, Essential dynamics (ED) derived from the MD trajectories of the three DNAs show that the backbone phosphate betwe en the two adenines complementary to the PD of the damaged DNA has con siderably larger mobility than the rest of the molecule and occurs onl y in the damaged DNA. As observed in the crystal structure of T4 endon uclease V in a complex with the damaged DNA, the interaction of the en zyme with the damaged DNA can lead to bending along the flexible joint and to induction of adenine flipping into an extra-helical position. Such motions may play an important role in damage recognition by repai r enzymes.