Zotchev S B, Protopopova M, Selivanova G
Microbiology and Tumour Biology Center, Karolinska Institutet, S-17177 Stockholm, Sweden.
Nucleic Acids Res. 2000 Oct 15;28(20):4005-12. doi: 10.1093/nar/28.20.4005.
In addition to binding DNA in a sequence-specific manner, the p53 tumour suppressor protein can interact with damaged DNA. In order to understand which structural features in DNA the C-teminal domain recognises we have studied the interaction of p53 protein with different types of DNA oligonucleotides imitating damaged DNA. Here we show that one unpaired nucleotide within double-stranded (ds)DNA is sufficient for recognition by the p53 C-terminus, either as a protruding end or as an internal gap in dsDNA. C-terminal interaction with DNA ends facilitated core domain binding to DNA, whereas interaction with gaps prevented core domain-DNA complexing, implying that p53 might adopt distinct conformations upon binding to different DNA lesions. These observations suggest that both single-strand and double-strand breaks can serve as a target for p53 C-terminal recognition in vivo and indicate that p53 might recruit different repair factors to the sites of damaged DNA depending on the type of lesion.
除了以序列特异性方式结合DNA外，p53肿瘤抑制蛋白还能与受损DNA相互作用。为了了解C末端结构域识别DNA中的哪些结构特征，我们研究了p53蛋白与模仿受损DNA的不同类型DNA寡核苷酸之间的相互作用。我们在此表明，双链（ds）DNA中的一个未配对核苷酸足以被p53 C末端识别，无论是作为突出端还是作为dsDNA中的内部缺口。与DNA末端的C末端相互作用促进了核心结构域与DNA的结合，而与缺口的相互作用则阻止了核心结构域与DNA的复合，这意味着p53在结合不同的DNA损伤时可能会采取不同的构象。这些观察结果表明，单链和双链断裂都可以作为p53 C末端在体内识别的靶点，并表明p53可能会根据损伤类型将不同的修复因子招募到受损DNA位点。
