P53 BINDS SINGLE-STRANDED-DNA ENDS AND CATALYZES DNA RENATURATION ANDSTRAND TRANSFER

The p53 tumor-suppressor protein has previously been shown to bind dou ble-stranded and single-stranded DNA. We report that the p53 protein c an bind single-stranded DNA ends and catalyze DNA renaturation and DNA strand transfer. Both a bacterially expressed wild-type p53 protein a nd a glutathione S-transferase-wild-type p53 fusion protein catalyzed renaturation of different short (25- to 76-nt) complementary single-st randed DNA fragments and promoted strand transfer between short (36-bp ) duplex DNA and complementary single-stranded DNA. Mutant p53 fusion proteins carrying amino acid substitutions Glu-213, Ile-237, or Tyr-23 8, derived from mutant p53 genes of Burkitt lymphomas, failed to catal yze these reactions. Wild-type p53 had significantly higher binding af finity for short (36- to 76-nt) than for longer (greater-than-or-equal -to 462-nt) single-stranded DNA fragments in an electrophoretic mobili ty-shift assay. Moreover, electron microscopy showed that p53 preferen tially binds single-stranded DNA ends. Binding of DNA ends to p53 olig omers may allow alignment of complementary strands. These findings sug gest that p53 may play a direct role in the repair of DNA breaks, incl uding the joining of complementary single-stranded DNA ends.