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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

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61988987%3A17310%2F19%3AA2002102" target="_blank" >RIV/61988987:17310/19:A2002102 - isvavai.cz</a>

  • Alternative codes found

    RIV/68081707:_____/19:00520186 RIV/00216224:14740/19:00110732 RIV/62157124:16370/19:43877652

  • Result on the web

    <a href="https://www.mdpi.com/1420-3049/24/11/2078" target="_blank" >https://www.mdpi.com/1420-3049/24/11/2078</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.3390/molecules24112078" target="_blank" >10.3390/molecules24112078</a>

Alternative languages

  • Result language

    angličtina

  • Original language 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

  • Original language description

    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.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10608 - Biochemistry and molecular biology

Result continuities

  • Project

    Result was created during the realization of more than one project. More information in the Projects tab.

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2019

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Molecules

  • ISSN

    1420-3049

  • e-ISSN

  • Volume of the periodical

    24

  • Issue of the periodical within the volume

    11

  • Country of publishing house

    CH - SWITZERLAND

  • Number of pages

    14

  • Pages from-to

  • UT code for WoS article

    000472631000051

  • EID of the result in the Scopus database