P53 BINDS SINGLE-STRANDED-DNA ENDS THROUGH THE C-TERMINAL DOMAIN AND INTERNAL DNA SEGMENTS VIA THE MIDDLE DOMAIN
P53 BINDS SINGLE-STRANDED-DNA ENDS THROUGH THE C-TERMINAL DOMAIN AND INTERNAL DNA SEGMENTS VIA THE MIDDLE DOMAIN
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DOI：
10.1093/nar/23.3.362
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发表时间：
1995-02-11
影响因子：
14.9
通讯作者：
WIMAN, KG
中科院分区：
文献类型：
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作者：
BAKALKIN, G;SELIVANOVA, G;WIMAN, KG
我们以前曾报道野生型p53可以结合单链（ss）DNA末端，并催化ss互补DNA分子的复性。在这里，我们证明，p53也可以通过结合位点（内部DNA位点）与DNA末端的结合位点（DNA末端位点）不同的SS DNA分子的内部片段结合。使用p53缺失突变体，将内部DNA位点定位于p53蛋白的中心区域（残基99-307），而将DNA末端位点定位于C-末端结构域（残基320-393）。内部DNA位点可以通过ss DNA末端与DNA末端位点的结合而被激活。单独的C-末端结构域足以催化DNA复性，尽管中心结构域也参与全长蛋白的复性促进。我们的研究结果表明，在体内DNA损伤产生的SS DNA末端的p53的C-末端尾部的相互作用可能会导致激活的p53的中心域的非特异性SS DNA结合。
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.