Bakalkin G, Selivanova G, Yakovleva T, Kiseleva E, Kashuba E, Magnusson K P, Szekely L, Klein G, Terenius L, Wiman K G
Department of Drug Dependence Research, Karolinska Institute, Stockholm, Sweden.
Nucleic Acids Res. 1995 Feb 11;23(3):362-9. doi: 10.1093/nar/23.3.362.
We have previously reported that wild-type p53 can bind single-stranded (ss) DNA ends and catalyze renaturation of ss complementary DNA molecules. Here we demonstrate that p53 can also bind to internal segments of ss DNA molecules via a binding site (internal DNA site) distinct from the binding site for DNA ends (DNA end site). Using p53 deletion mutants, the internal DNA site was mapped to the central region (residues 99-307), while the DNA end site was mapped to the C-terminal domain (residues 320-393) of the p53 protein. The internal DNA site can be activated by the binding of ss DNA ends to the DNA end site. The C-terminal domain alone was sufficient to catalyze DNA renaturation, although the central domain was also involved in promotion of renaturation by the full-length protein. Our results suggest that the interaction of the C-terminal tail of p53 with ss DNA ends generated by DNA damage in vivo may lead to activation of non-specific ss DNA binding by the central domain of p53.
我们之前报道过，野生型p53能够结合单链（ss）DNA末端并催化ss互补DNA分子的复性。在此我们证明，p53还能通过一个不同于DNA末端结合位点（DNA末端位点）的结合位点（内部DNA位点）与ss DNA分子的内部片段结合。利用p53缺失突变体，内部DNA位点被定位到中央区域（第99 - 307位氨基酸残基），而DNA末端位点被定位到p53蛋白的C末端结构域（第320 - 393位氨基酸残基）。内部DNA位点可通过ss DNA末端与DNA末端位点的结合而被激活。单独的C末端结构域就足以催化DNA复性，尽管中央结构域也参与全长蛋白对复性的促进作用。我们的结果表明，p53的C末端尾巴与体内DNA损伤产生的ss DNA末端之间的相互作用，可能会导致p53中央结构域非特异性ss DNA结合的激活。
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