A new class of DNA glycosylase/apurinic/apyrimidinic lyases that act on specific adenines in single-stranded DNA.
Although the biological function of DNA glycosylases is to protect the genome by removal of potentially cytotoxic or mutagenic bases, this investigation describes the existence of natural DNA glycosylases with activity on undamaged, nonmispaired bases. Gelonin, pokeweed antiviral protein, and ricin, previously described as ribosome-inactivating proteins, are shown to damage single-stranded DNA by removal of a protein-specific set of adenines and cleavage at the resulting abasic sites. Using an oligonucleotide as the substrate reveals that the reaction proceeds via the enzyme-DNA imino intermediate characteristic of DNA glycosylase/AP lyases. The adenine glycosylase activity on single-stranded DNA reported here challenges the concept that a normal base has to be in a mismatch to be specifically removed. By contrast to other glycosylases, these enzymes are expected to damage DNA rather than participate in repair processes. The significance of this DNase activity to the biological function of these plant proteins and to their toxicity to animal cells remains to be determined.
Nicolas
E
E
Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA.
Beggs
J M
JM
Haltiwanger
B M
BM
Taraschi
T F
TF
D000225:Adenine / Q000378:metabolism*; D001483:Base Sequence; D019757:Carbon-Oxygen Lyases / Q000378:metabolism*; D045647:DNA Glycosylases; D004277:DNA, Single-Stranded / Q000378:metabolism*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D043223:Deoxyribonuclease IV (Phage T4-Induced); D006868:Hydrolysis; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D013379:Substrate Specificity
D004277:DNA, Single-Stranded; D009838:Oligodeoxyribonucleotides; D043223:Deoxyribonuclease IV (Phage T4-Induced); D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D019757:Carbon-Oxygen Lyases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D000225:Adenine