G. Bakalkin et al., P53 BINDS SINGLE-STRANDED-DNA ENDS AND CATALYZES DNA RENATURATION ANDSTRAND TRANSFER, Proceedings of the National Academy of Sciences of the United Statesof America, 91(1), 1994, pp. 413-417
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.