The structure formed by inverted repeats in p53 response elements determines the transactivation activity of p53 protein

0485751 - BFÚ 2018 RIV US eng J - Journal Article
Brázda, Václav - Čechová, Jana - Battistin, M. - Coufal, Jan - Jagelská, Eva - Raimondi, I. - Inga, A.
The structure formed by inverted repeats in p53 response elements determines the transactivation activity of p53 protein.
Biochemical and Biophysical Research Communications. Roč. 483, č. 1 (2017), s. 516-521. ISSN 0006-291X. E-ISSN 1090-2104
R&D Projects: GA ČR GA15-21855S
Institutional support: RVO:68081707
Keywords : tumor-suppressor p53 * cruciform structures * dna-conformation
OECD category: Biochemistry and molecular biology
Impact factor: 2.559, year: 2017

The TP53 gene is the most frequently mutated gene in human cancer and p53 protein plays a crucial role in gene expression and cancer protection. Its role is manifested by interactions with other proteins and DNA. p53 is a transcription factor that binds to DNA response elements (REs). Due to the palindromic nature of the consensus binding site, several p53-REs have the potential to form cruciform structures. However, the influence of cruciform formation on the activity of p53-REs has not been evaluated. Therefore, we prepared sets of p53-REs with identical theoretical binding affinity in their linear state, but different probabilities to form extra helical structures, for in vitro and in vivo analyses. Then we evaluated the presence of cruciform structures when inserted into plasmid DNA and employed a yeast-based assay to measure transactivation potential of these p53-REs cloned at a chromosomal locus in isogenic strains. We show that transactivation in vivo correlated more with relative propensity of an RE to form cruciforms than to its predicted in vitro DNA binding affinity for wild type p53. Structural features of p53-REs could therefore be an important determinant of p53 transactivation function. (C) 2016 Elsevier Inc. All rights reserved.
Permanent Link: http://hdl.handle.net/11104/0280695