title: The repair of pyrimidine dimers via a DNA-glycosylase mechanism.
abstract: The "UV endonuclease" isolated either from M. luteus or bacteriophage T4 infected E. coli (the denV gene product) consists of two enzymatic activities on a single polypeptide chain: a pyrimidine dimer-DNA glycosylase and an AP endonuclease. The repair of pyrimidine dimers by this enzyme is initiated by the cleavage of the N-glycosylic bond of the 5' pyrimidine of the dimer that leaves the cyclobutane dimer still attached to the DNA through the N-glycosylic bond of the 3' pyrimidine of the dimer. This reaction results in the formation of an apyrimidinic site in the DNA. The second step in this repair pathway is the endonucleolytic cleavage of the DNA 3' to the AP site by the associated AP endonuclease. As a result, the nicked DNA contains DNA damage on both sides of the incision site: an apyrimidinic moiety on the 3' end and a thymine-thymidylate dimer on the 5' end. The enzymes prefer double stranded DNA over single stranded DNA, and thymine over cytosine at the 5' position of the dimer. The AP endonuclease activity prefers the AP site created by the pyrimidine dimer-DNA glycosylase on UV irradiated DNA over either apurinic or apyrimidinic DNA. This repair mechanism appears to be operative in vivo since DNA intermediates containing thymine-thymidylate dimer sites have been detected in UV irradiated T4 infected E. coli and in UV irradiated M. luteus. The cloned denV gene partially complements the UV repair deficient uvr A, B, C strains of E. coli.
mesh_terms: D003001:Cloning, Molecular; D045647:DNA Glycosylases; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D043223:Deoxyribonuclease IV (Phage T4-Induced); D004706:Endodeoxyribonucleases / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics / Q000528:radiation effects; D029968:Escherichia coli Proteins; D005796:Genes / Q000528:radiation effects; D008837:Micrococcus / Q000201:enzymology / Q000235:genetics* / Q000528:radiation effects; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D011740:Pyrimidine Dimers / Q000378:metabolism*; D013604:T-Phages / Q000201:enzymology / Q000235:genetics* / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D029968:Escherichia coli Proteins; D011740:Pyrimidine Dimers; D004706:Endodeoxyribonucleases; D043223:Deoxyribonuclease IV (Phage T4-Induced); C468972:endonuclease IV, E coli; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; C036401:deoxyribopyrimidine endonucleosidase; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase