Petr Marek, Helma Robert, Polášková Alena, Krejčí Aneta, Dvořáková Zuzana, Kejnovská Iva, Navrátilová Lucie, Adámik Matej, Vorlíčková Michaela, Brázdová Marie
Department of Biophysical Chemistry and Molecular Oncology, Institute of Biophysics, The Czech Academy of Sciences, Královopolská 135, 612 65 Brno, Czech Republic.
Department of CD Spectroscopy of Nucleic Acids, Institute of Biophysics, The Czech Academy of Sciences, Královopolská 135, 612 65 Brno, Czech Republic.
Biosci Rep. 2016 Oct 14;36(5). doi: 10.1042/BSR20160232. Print 2016 Oct.
G-quadruplexes are four-stranded nucleic acid structures that are implicated in the regulation of transcription, translation and replication. Genome regions enriched in putative G-quadruplex motifs include telomeres and gene promoters. Tumour suppressor p53 plays a critical role in regulatory pathways leading to cell cycle arrest, DNA repair and apoptosis. In addition to transcriptional regulation mediated via sequence-specific DNA binding, p53 can selectively bind various non-B DNA structures. In the present study, wild-type p53 (wtp53) binding to G-quadruplex formed by MYC promoter nuclease hypersensitive element (NHE) III region was investigated. Wtp53 binding to MYC G-quadruplex is comparable to interaction with specific p53 consensus sequence (p53CON). Apart from the full-length wtp53, its isolated C-terminal region (aa 320-393) as well, is capable of high-affinity MYC G-quadruplex binding, suggesting its critical role in this type of interaction. Moreover, wtp53 binds to MYC promoter region containing putative G-quadruplex motif in two wtp53-expressing cell lines. The results suggest that wtp53 binding to G-quadruplexes can take part in transcriptional regulation of its target genes.
G-四链体是四链核酸结构,与转录、翻译和复制的调控有关。富含假定G-四链体基序的基因组区域包括端粒和基因启动子。肿瘤抑制因子p53在导致细胞周期停滞、DNA修复和细胞凋亡的调控途径中起关键作用。除了通过序列特异性DNA结合介导的转录调控外,p53还能选择性地结合各种非B型DNA结构。在本研究中,研究了野生型p53(wtp53)与由MYC启动子核酸酶超敏元件(NHE)III区形成的G-四链体的结合。Wtp53与MYC G-四链体的结合与与特定p53共有序列(p53CON)的相互作用相当。除了全长wtp53外,其分离的C末端区域(氨基酸320-393)也能够高亲和力结合MYC G-四链体,表明其在这种类型的相互作用中起关键作用。此外,wtp53在两个表达wtp53的细胞系中与含有假定G-四链体基序的MYC启动子区域结合。结果表明,wtp53与G-四链体的结合可以参与其靶基因的转录调控。