TY - JOUR
T1 - Essential dynamics of DNA containing a cis.syn cyclobutane thymine dimer lesion
AU - Yamaguchi, Hiroshi
AU - Van Aalten, Daan M.F.
AU - Pinak, Miroslav
AU - Furukawa, Akira
AU - Osman, Roman
N1 - Funding Information:
H.Y is grateful to the Department of Physiology and Biophysics of Mount Sinai School of Medicine for their hospitality. Professor A.C.T.North of the University of Leeds is acknowledged for his help in ED analysis of DNA and Mr D.Akrigg for his arrangement of the computer environment at the University of Leeds. Mr S.Hongo and Mr H.Takeshita at the National Institute of Radiological Sciences are acknowledged for their help with the computational resources during this work. This work was supported by grants from the Science Technology Agency Japan, the British Council and NIH grant CA 66317 (to R.O.).
PY - 1998/4/15
Y1 - 1998/4/15
N2 - Conformational properties of a UV-damaged DNA decamer containing a cis.syn cyclobutane thymine dimer (PD) have been investigated by molecular dynamics (MD) simulations. Results from MD simulations of the damaged decamer DNA show a kink of ~21.7°at the PD damaged site and a disruption of H bonding between the 5'-thymine of the PD and its complementary adenine. However, no extra-helical flipping of the 3'-adenine complementary to the PD was observed. Comparison to two undamaged DNA decamers, one with the same sequence and the other with an AT replacing the TT sequence, indicates that these properties are specific to the damaged DNA. Essential dynamics (ED) derived from the MD trajectories of the three DNAs show that the backbone phosphate between the two adenines complementary to the PD of the damaged DNA has considerably larger mobility than the rest of the molecule and occurs only in the damaged DNA. As observed in the crystal structure of T4 endonuclease V in a complex with the damaged DNA, the interaction of the enzyme 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 repair enzymes.
AB - Conformational properties of a UV-damaged DNA decamer containing a cis.syn cyclobutane thymine dimer (PD) have been investigated by molecular dynamics (MD) simulations. Results from MD simulations of the damaged decamer DNA show a kink of ~21.7°at the PD damaged site and a disruption of H bonding between the 5'-thymine of the PD and its complementary adenine. However, no extra-helical flipping of the 3'-adenine complementary to the PD was observed. Comparison to two undamaged DNA decamers, one with the same sequence and the other with an AT replacing the TT sequence, indicates that these properties are specific to the damaged DNA. Essential dynamics (ED) derived from the MD trajectories of the three DNAs show that the backbone phosphate between the two adenines complementary to the PD of the damaged DNA has considerably larger mobility than the rest of the molecule and occurs only in the damaged DNA. As observed in the crystal structure of T4 endonuclease V in a complex with the damaged DNA, the interaction of the enzyme 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 repair enzymes.
UR - http://www.scopus.com/inward/record.url?scp=0032522136&partnerID=8YFLogxK
U2 - 10.1093/nar/26.8.1939
DO - 10.1093/nar/26.8.1939
M3 - Article
C2 - 9518486
AN - SCOPUS:0032522136
SN - 0305-1048
VL - 26
SP - 1939
EP - 1946
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 8
ER -