Twist and turn: a revised structural view on the unpaired bubble of class II CPD photolyase in complex with damaged DNA
Abstract
Cyclobutane pyrimidine dimer (CPD) photolyases harness the energy of blue light to repair UV-induced DNA CPDs. Upon binding, CPD photolyases cause the photodamage to flip out of the duplex DNA and into the catalytic site of the enzyme. This process, called base-flipping, induces a kink in the DNA, as well as an unpaired bubble, which are stabilized by a network of protein–nucleic acid interactions. Previously, several co-crystal structures have been reported in which the binding mode of CPD photolyases has been studied in detail. However, in all cases the internucleoside linkage of the photodamage site was a chemically synthesized formacetal analogue and not the natural phosphodiester. Here, the first crystal structure and conformational analysis via molecular-dynamics simulations of a class II CPD photolyase in complex with photodamaged DNA that contains a natural cyclobutane pyrimidine dimer with an intra-lesion phosphodiester linkage are presented. It is concluded that a highly conserved bubble-intruding region (BIR) mediates stabilization of the open form of CPD DNA when complexed with class II CPD photolyases.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 08, 2018
- Source ID
- 10.1107/s205225251800996x
Entities
People
- Junpei Yamamoto
- Lars-Oliver Essen
- Manuel Maestre-Reyna
- Ming-Daw Tsai
- Wei-Cheng Huang
- Yoshitaka Bessho
Organizations
- Air Force Office of Scientific Research
- National Science and Technology Council