Clarifying functions of the p53 protein is a crucial aspect of cancer research. We analyzed the binding sites of p53 wild-type (WT) protein and its oncologically significant mutants and evaluated their transactivation properties using a functional yeast assay. Unlike the binding sites as determined in myeloid leukemia cell lines by chromatin immunoprecipitation of p53-R175H, p53-Y220C, p53-M237I, p53-R248Q, and p53-R273H mutants, the target sites of p53-WT and p53-R282W were significantly associated with putative G-quadruplex sequences (PQSs). Guanine-quadruplex (G-quadruplex or G4) formation in these sequences was evaluated by using a set of biophysical methods. G4s can modulate gene expression induced by p53. At low p53 expression level, PQS upstream of the p53-response element (RE) leads to greater gene expression induced by p53-R282W compared to that for the RE without PQS. Meanwhile, p53-WT protein expression is decreased by the PQS presence. At a high p53 expression level, the presence of PQS leads to a decreased expression of the reporter regardless of the distance and localization of the G4 from the RE.

• Publikační typ
• časopisecké články MeSH

Nucleic acid-binding proteins are traditionally divided into two categories: With the ability to bind DNA or RNA. In the light of new knowledge, such categorizing should be overcome because a large proportion of proteins can bind both DNA and RNA. Another even more important features of nucleic acid-binding proteins are so-called sequence or structure specificities. Proteins able to bind nucleic acids in a sequence-specific manner usually contain one or more of the well-defined structural motifs (zinc-fingers, leucine zipper, helix-turn-helix, or helix-loop-helix). In contrast, many proteins do not recognize nucleic acid sequence but rather local DNA or RNA structures (G-quadruplexes, i-motifs, triplexes, cruciforms, left-handed DNA/RNA form, and others). Finally, there are also proteins recognizing both sequence and local structural properties of nucleic acids (e.g., famous tumor suppressor p53). In this mini-review, we aim to summarize current knowledge about the amino acid composition of various types of nucleic acid-binding proteins with a special focus on significant enrichment and/or depletion in each category.

• Klíčová slova
• DNA, G-quadruplex, RNA, Z-DNA, Z-RNA, amino acid composition, cruciform, i-motif, protein binding, triplex,
• MeSH
• DNA vazebné proteiny genetika   MeSH
• DNA genetika   ultrastruktura   MeSH
• G-kvadruplexy MeSH
• konformace nukleové kyseliny * MeSH
• leucinové zipy genetika   MeSH
• lidé MeSH
• nukleoproteiny genetika   ultrastruktura   MeSH
• RNA chemie   ultrastruktura   MeSH
• sekvence aminokyselin genetika   MeSH
• transportní proteiny genetika   ultrastruktura   MeSH
• Z-DNA MeSH
• zinkové prsty genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• DNA vazebné proteiny MeSH
• DNA MeSH
• nukleoproteiny MeSH
• RNA MeSH
• transportní proteiny MeSH
• Z-DNA MeSH

p53 is one of the most studied tumor suppressor proteins that plays an important role in basic biological processes including cell cycle, DNA damage response, apoptosis, and senescence. The human TP53 gene contains alternative promoters that produce N-terminally truncated proteins and can produce several isoforms due to alternative splicing. p53 function is realized by binding to a specific DNA response element (RE), resulting in the transactivation of target genes. Here, we evaluated the influence of quadruplex DNA structure on the transactivation potential of full-length and N-terminal truncated p53α isoforms in a panel of S. cerevisiae luciferase reporter strains. Our results show that a G-quadruplex prone sequence is not sufficient for transcription activation by p53α isoforms, but the presence of this feature in proximity to a p53 RE leads to a significant reduction of transcriptional activity and changes the dynamics between co-expressed p53α isoforms.

• Klíčová slova
• p53 protein, protein-DNA interaction, transactivation potential,
• MeSH
• G-kvadruplexy * MeSH
• lidé MeSH
• nádorový supresorový protein p53 genetika   metabolismus   MeSH
• promotorové oblasti (genetika) genetika   MeSH
• protein - isoformy genetika   metabolismus   MeSH
• proteiny regulující apoptózu genetika   metabolismus   MeSH
• protoonkogenní proteiny genetika   metabolismus   MeSH
• responzivní elementy genetika   MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• BBC3 protein, human MeSH Prohlížeč
• nádorový supresorový protein p53 MeSH
• protein - isoformy MeSH
• proteiny regulující apoptózu MeSH
• protoonkogenní proteiny MeSH

The tumor suppressor functions of p53 and its roles in regulating the cell cycle, apoptosis, senescence, and metabolism are accomplished mainly by its interactions with DNA. p53 works as a transcription factor for a significant number of genes. Most p53 target genes contain so-called p53 response elements in their promoters, consisting of 20 bp long canonical consensus sequences. Compared to other transcription factors, which usually bind to one concrete and clearly defined DNA target, the p53 consensus sequence is not strict, but contains two repeats of a 5'RRRCWWGYYY3' sequence; therefore it varies remarkably among target genes. Moreover, p53 binds also to DNA fragments that at least partially and often completely lack this consensus sequence. p53 also binds with high affinity to a variety of non-B DNA structures including Holliday junctions, cruciform structures, quadruplex DNA, triplex DNA, DNA loops, bulged DNA, and hemicatenane DNA. In this review, we summarize information of the interactions of p53 with various DNA targets and discuss the functional consequences of the rich world of p53 DNA binding targets for its complex regulatory functions.

• Klíčová slova
• consensus sequence, cruciform, local DNA structures, p53, protein-DNA interactions,
• MeSH
• DNA chemie   metabolismus   MeSH
• konformace nukleové kyseliny MeSH
• konformace proteinů MeSH
• konsenzuální sekvence MeSH
• lidé MeSH
• molekulární modely MeSH
• nádorový supresorový protein p53 chemie   metabolismus   MeSH
• sekvence aminokyselin MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• DNA MeSH
• nádorový supresorový protein p53 MeSH

Expansions of trinucleotide repeats (TNRs) are associated with genetic disorders such as Friedreich's ataxia. The tumor suppressor p53 is a central regulator of cell fate in response to different types of insults. Sequence and structure-selective modes of DNA recognition are among the main attributes of p53 protein. The focus of this work was analysis of the p53 structure-selective recognition of TNRs associated with human neurodegenerative diseases. Here, we studied binding of full length p53 and several deletion variants to TNRs folded into DNA hairpins or loops. We demonstrate that p53 binds to all studied non-B DNA structures, with a preference for non-B DNA structures formed by pyrimidine (Py) rich strands. Using deletion mutants, we determined the C-terminal DNA binding domain of p53 to be crucial for recognition of such non-B DNA structures. We also observed that p53 in vitro prefers binding to the Py-rich strand over the purine (Pu) rich strand in non-B DNA substrates formed by sequence derived from the first intron of the frataxin gene. The binding of p53 to this region was confirmed using chromatin immunoprecipitation in human Friedreich's ataxia fibroblast and adenocarcinoma cells. Altogether these observations provide further evidence that p53 binds to TNRs' non-B DNA structures.

• Klíčová slova
• DNA hairpin, DNA–protein, frataxin, non-B DNA, p53, trinucleotide repeat,
• MeSH
• DNA chemie   metabolismus   MeSH
• expanze trinukleotidových repetic * MeSH
• exprese genu MeSH
• Friedreichova ataxie genetika   metabolismus   MeSH
• interakční proteinové domény a motivy MeSH
• konformace nukleové kyseliny * MeSH
• lidé MeSH
• nádorový supresorový protein p53 chemie   metabolismus   MeSH
• pyrimidiny MeSH
• rekombinantní proteiny MeSH
• trinukleotidové repetice * MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA MeSH
• nádorový supresorový protein p53 MeSH
• pyrimidiny MeSH
• rekombinantní proteiny MeSH
• TP53 protein, human MeSH Prohlížeč

p53 plays critical roles in regulating cell cycle, apoptosis, senescence and metabolism and is commonly mutated in human cancer. These roles are achieved by interaction with other proteins, but particularly by interaction with DNA. As a transcription factor, p53 is well known to bind consensus target sequences in linear B-DNA. Recent findings indicate that p53 binds with higher affinity to target sequences that form cruciform DNA structure. Moreover, p53 binds very tightly to non-B DNA structures and local DNA structures are increasingly recognized to influence the activity of wild-type and mutant p53. Apart from cruciform structures, p53 binds to quadruplex DNA, triplex DNA, DNA loops, bulged DNA and hemicatenane DNA. In this review, we describe local DNA structures and summarize information about interactions of p53 with these structural DNA motifs. These recent data provide important insights into the complexity of the p53 pathway and the functional consequences of wild-type and mutant p53 activation in normal and tumor cells.

• Klíčová slova
• local DNA structures, p53 protein, protein-DNA interactions,
• MeSH
• B-DNA MeSH
• DNA chemie   genetika   metabolismus   MeSH
• konformace nukleové kyseliny * MeSH
• lidé MeSH
• nádorový supresorový protein p53 chemie   metabolismus   MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• B-DNA MeSH
• DNA MeSH
• nádorový supresorový protein p53 MeSH
• triplex DNA MeSH Prohlížeč