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

J 2019

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, R., P. BAZANTOVA, M. PETR, M. ADAMIK, D. RENCIUK et. al.

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

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

Abstract

V originále

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 MU

Name: 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

Citovat

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. 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.

@article{1559616,
   author = {Helma, R. and Bazantova, P. and Petr, M. and Adamik, M. and Renciuk, D. and Tichy, V. and Pastuchova, A. and Soldanova, Z. and Pecinka, P. and Bowater, R.P. and Fojta, Miroslav and Brazdova, M.},
   article_location = {BASEL},
   article_number = {11},
   doi = {http://dx.doi.org/10.3390/molecules24112078},
   keywords = {trinucleotide repeat; p53; non-B DNA; DNA hairpin; DNA-protein; frataxin},
   language = {eng},
   issn = {1420-3049},
   journal = {Molecules},
   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},
   url = {https://www.mdpi.com/1420-3049/24/11/2078},
   volume = {24},
   year = {2019}
}

TY  - JOUR
ID  - 1559616
AU  - Helma, R. - Bazantova, P. - Petr, M. - Adamik, M. - Renciuk, D. - Tichy, V. - Pastuchova, A. - Soldanova, Z. - Pecinka, P. - Bowater, R.P. - Fojta, Miroslav - Brazdova, M.
PY  - 2019
TI  - 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
JF  - Molecules
VL  - 24
IS  - 11
SP  - 2078
EP  - 2078
PB  - Mayer und Muller
SN  - 14203049
KW  - trinucleotide repeat
KW  - p53
KW  - non-B DNA
KW  - DNA hairpin
KW  - DNA-protein
KW  - frataxin
UR  - https://www.mdpi.com/1420-3049/24/11/2078
L2  - https://www.mdpi.com/1420-3049/24/11/2078
N2  - 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.
ER  -

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. \textit{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.

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