P53 PROTEIN EXHIBITS 3'-TO-5' EXONUCLEASE ACTIVITY

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 exo nuclease activity is intrinsic to the wild-type p53 protein: it copuri fied with p53 during p53 preparation; only purified wild-type p53, but not identically purified mutant p53 proteins displayed exonuclease ac tivity; the exonuclease activity could be reconstituted from SDS gel-p urified and urea-renatured p53 protein and mapped to the core domain o f the p53 molecule; and finally, purified p53 protein could be UV cros s-linked to GMP. A p53-intrinsic exonuclease activity should substanti ally extend our view on the role of p53 as a ''guardian of the genome. ''