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

Helma, Robert; Bažantová, Pavla; Petr, Marek; Adámik, Matěj; Renčiuk, Daniel; Tichý, Vlastimil; Pastuchová, Alena; Soldanová, Zuzana; Pečinka, Petr; Bowater, R. P.; Fojta, Miroslav; Brázdová, Marie

doi:https://dx.doi.org/10.3390/molecules24112078

Number of the records: 1

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

1.

SYSNO ASEP	0520186
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	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
Author(s)	Helma, Robert (BFU-R)_ORCID Bažantová, Pavla (BFU-R) Petr, Marek (BFU-R)_ORCID Adámik, Matěj (BFU-R)_ORCID Renčiuk, Daniel (BFU-R)_{RID, ORCID} Tichý, Vlastimil (BFU-R)_RID Pastuchová, Alena (BFU-R)_ORCID Soldanová, Zuzana (BFU-R)_ORCID Pečinka, Petr (BFU-R)_RID Bowater, R. P. (GB) Fojta, Miroslav (BFU-R)_{RID, ORCID} Brázdová, Marie (BFU-R)_{RID, ORCID}
Number of authors	12
Article number	2078
Source Title	Molecules. - : MDPI Roč. 24, č. 11 (2019)
Number of pages	14 s.
Publication form	Online - E
Language	eng - English
Country	CH - Switzerland
Keywords	dynamic mutations ; disease ; length
Subject RIV	CE - Biochemistry
OECD category	Biochemistry and molecular biology
R&D Projects	GA19-15168S GA ČR - Czech Science Foundation (CSF)
	GA16-01625S GA ČR - Czech Science Foundation (CSF)
	GJ17-19170Y GA ČR - Czech Science Foundation (CSF)
	EF15_003/0000477 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
Method of publishing	Open access
Institutional support	BFU-R - RVO:68081707
UT WOS	000472631000051
DOI	10.3390/molecules24112078
Annotation	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.
Workplace	Institute of Biophysics
Contact	Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244
Year of Publishing	2020
Electronic address	https://www.mdpi.com/1420-3049/24/11/2078/pdf

Number of the records: 1