Specific interaction between damaged bases in DNA and repair enzymes

T4 endonuclease V is a DNA repair enzyme from bacteriophage T4 which catalyzes the first reaction step of the pyrimidine dimer specific base excision repair pathway. The crystal structure of the enzyme complexed with a duplex DNA substrate, containing a thymine dimer, has been determined at 2.75 Angstrom resolution. The atomic structure of the complex reveals the unique conformation of the DNA duplex, which exhibits a sharp kink with a 60 degrees inclination at the central thymine dimer. This kink divides the duplex into two B-DNA regions, each of which makes extensive polar interactions with the basic concave surface of the enzyme. The adenine base complementary to the 5' side of the thymine dimer is completely flipped out of the DNA duplex and is trapped in a cavity on the protein surface. These structural features allow an understanding of the catalytic mechanism and implicate a general mechanism of how other repair enzymes recognize damaged DNA duplexes.