Recognition of damaged regions in DNA by oligopeptides and proteins.
The binding of various damaged DNAs to the single-strand binding protein coded for by gene 32 from bacteriophage T4, on the one hand, and of oligopeptides containing tryptophan and lysine residues, on the other hand, is described. These molecules exhibit a higher affinity for modified DNA than for native DNA in so far as modification results in a local destabilization of the double-stranded structure of the nucleic acid. Stacking interactions between aromatic amino acids and nucleic acid bases appear to play a crucial role in the recognition of destabilized regions induced by chemical agents (carcinogens and antitumor drugs). These interactions confer to the peptide lysyl-tryptophyl-lysine an endonucleolytic activity specific for apurinic sites. From results obtained with such oligopeptides a model for the active sites of Ap-endonucleases is proposed which could account for the strategy used by the denV endonuclease from phage T4 during the first step of excision repair of pyrimidine dimers in DNA. The effect of the overall conformation of modified DNA on repair efficiency is discussed.
J J
JJ
Toulmé
T S
TS
Saison-Behmoaras
D000596:Amino Acids / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000378:metabolism* / Q000528:radiation effects; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000378:metabolism; D004278:DNA, Superhelical / Q000378:metabolism; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D043223:Deoxyribonuclease IV (Phage T4-Induced); D004706:Endodeoxyribonucleases / Q000378:metabolism; D009690:Nucleic Acid Conformation; D009842:Oligopeptides / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014466:Ultraviolet Rays; D014764:Viral Proteins / Q000378:metabolism
D000596:Amino Acids; D004277:DNA, Single-Stranded; D004278:DNA, Superhelical; D009842:Oligopeptides; D011506:Proteins; D014764:Viral Proteins; D004247:DNA; D004706:Endodeoxyribonucleases; D043223:Deoxyribonuclease IV (Phage T4-Induced); C026044:deoxyribonuclease V; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase