HELMA, R., P. BAZANTOVA, M. PETR, M. ADAMIK, D. RENCIUK, V. TICHY, A. PASTUCHOVA, Z. SOLDANOVA, P. PECINKA, R.P. BOWATER, Miroslav FOJTA and M. BRAZDOVA. p53 Binds Preferentially to Non-B DNA Structures Formed by the Pyrimidine-Rich Strands of GAA center dot TTC Trinucleotide Repeats Associated with Friedreich's Ataxia. Online. Molecules. BASEL: Mayer und Muller, 2019, vol. 24, No 11, p. 2078-2091. ISSN 1420-3049. Available from: https://dx.doi.org/10.3390/molecules24112078. [citováno 2024-04-24]
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Basic information
Original name p53 Binds Preferentially to Non-B DNA Structures Formed by the Pyrimidine-Rich Strands of GAA center dot TTC Trinucleotide Repeats Associated with Friedreich's Ataxia
Authors HELMA, R. (203 Czech Republic), P. BAZANTOVA (203 Czech Republic), M. PETR (203 Czech Republic), M. ADAMIK (203 Czech Republic), D. RENCIUK (203 Czech Republic), V. TICHY (203 Czech Republic), A. PASTUCHOVA (203 Czech Republic), Z. SOLDANOVA (203 Czech Republic), P. PECINKA (203 Czech Republic), R.P. BOWATER (826 United Kingdom of Great Britain and Northern Ireland), Miroslav FOJTA (203 Czech Republic, guarantor, belonging to the institution) and M. BRAZDOVA (203 Czech Republic)
Edition Molecules, BASEL, Mayer und Muller, 2019, 1420-3049.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10608 Biochemistry and molecular biology
Country of publisher Switzerland
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 3.267
RIV identification code RIV/00216224:14740/19:00110732
Organization unit Central European Institute of Technology
Doi http://dx.doi.org/10.3390/molecules24112078
UT WoS 000472631000051
Keywords in English trinucleotide repeat; p53; non-B DNA; DNA hairpin; DNA-protein; frataxin
Tags BISON, rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Pavla Foltynová, Ph.D., učo 106624. Changed: 13/2/2020 13:23.
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.
Links
692068, interní kód MUName: BISON - Bridging Structural Biology with Biological Synthesis and Self Assembly to Reveal Key Processes in Living Systems (Acronym: BISON)
Investor: European Union, Spreading excellence and widening participation
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