ATOMIC MODEL OF A PYRIMIDINE DIMER EXCISION-REPAIR ENZYME COMPLEXED WITH A DNA SUBSTRATE - STRUCTURAL BASIS FOR DAMAGED DNA RECOGNITION

T4 endonuclease V is a DNA repair enzyme from bacteriophage T4 that ca talyzes the first reaction step of the pyrimidine dimer-specific base excision repair pathway. The crystal structure of this enzyme complexe d with a duplex DNA substrate, containing a thymine dimer, has been de termined at 2.75 Angstrom resolution, The atomic structure of the comp lex reveals the unique conformation of the DNA duplex, which exhibits a sharp kink with a 60 degrees inclination at the central thymine dime r, The adenine base complementary to the 5' side of the thymine dimer is completely flipped out of the DNA duplex and 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 o ther repair enzymes recognize damaged DNA duplexes.