title: p53 Protein exhibits 3'-to-5' exonuclease activity.
abstract: Highly purified p53 protein from different sources was able to degrade DNA with a 3'-to-5' polarity, yielding deoxynucleoside monophosphates as reaction products. This exonuclease activity was dependent on Mg2+ and inhibited by addition of 5 mM nucleoside monophosphates. This exonuclease activity is intrinsic to the wild-type p53 protein: it copurified with p53 during p53 preparation; only purified wild-type p53, but not identically purified mutant p53 proteins displayed exonuclease activity; the exonuclease activity could be reconstituted from SDS gel-purified and urea-renatured p53 protein and mapped to the core domain of the p53 molecule; and finally, purified p53 protein could be UV-cross-linked to GMP. A p53-intrinsic exonuclease activity should substantially extend our view on the role of p53 as a "guardian of the genome."
authors.affiliation: Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, Hamburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Mummenbrauer
authors.forename: F
authors.initials: F
authors.lastname: Janus
authors.forename: B
authors.initials: B
authors.lastname: Müller
authors.forename: L
authors.initials: L
authors.lastname: Wiesmüller
authors.forename: W
authors.initials: W
authors.lastname: Deppert
authors.forename: F
authors.initials: F
authors.lastname: Grosse
mesh_terms: D000911:Antibodies, Monoclonal; D001483:Base Sequence; D002846:Chromatography, Affinity; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins / Q000378:metabolism; D015224:Dideoxynucleosides / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005092:Exonucleases / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D006157:Guanosine Monophosphate / Q000378:metabolism; D006801:Humans; D008274:Magnesium / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D015224:Dideoxynucleosides; D016159:Tumor Suppressor Protein p53; D006157:Guanosine Monophosphate; D005092:Exonucleases; D008274:Magnesium