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Helma, Robert, Bažantová, Pavla, Petr, Marek, Adámik, Matej, Renčiuk, Daniel, Tichý, Vlastimil, Pastuchová, Alena, Soldánová, Zuzana, Pečinka, Petr, Bowater, Richard P. 
ORCID: https://orcid.org/0000-0002-2745-7807, Fojta, Miroslav and Brázdová, Marie
(2019)
P53 binds preferentially to non-B DNA structures formed by the pyrimidine-rich strands of GaA·TTC trinucleotide repeats associated with Friedreich’s ataxia.
Molecules, 24 (11).
ISSN 1420-3049
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Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | dna hairpin,dna–protein,frataxin,non-b dna,p53,trinucleotide repeat,analytical chemistry,chemistry (miscellaneous),molecular medicine,pharmaceutical science,drug discovery,physical and theoretical chemistry,organic chemistry,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1600/1602 |
| Faculty \ School: | Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Science > Research Groups > Molecular Microbiology Faculty of Science > Research Centres > Centre for Molecular and Structural Biochemistry Faculty of Science > Research Groups > Biosciences Teaching and Education Research |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 17 Jun 2019 08:30 |
| Last Modified: | 20 Apr 2023 07:33 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/71402 |
| DOI: | 10.3390/molecules24112078 |
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