p53 C-terminal interaction with DNA ends and gaps has opposing effect on specific DNA binding by the core.
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.
Zotchev
S B
SB
Microbiology and Tumour Biology Center, Karolinska Institutet, S-17177 Stockholm, Sweden.
Protopopova
M
M
Selivanova
G
G
D020029:Base Pairing / Q000235:genetics; D001483:Base Sequence; D001667:Binding, Competitive; D004247:DNA / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D004249:DNA Damage / Q000235:genetics*; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009711:Nucleotides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion / Q000235:genetics*; D013379:Substrate Specificity; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*
D004277:DNA, Single-Stranded; D009711:Nucleotides; D009838:Oligodeoxyribonucleotides; D016159:Tumor Suppressor Protein p53; D004247:DNA