DNA i-motif formation at neutral pH is driven by kinetic
partitioning

J 2023

DNA i-motif formation at neutral pH is driven by kinetic partitioning

ŠKOLÁKOVÁ, Petra, Martin GAJARSKÝ, Jan PALACKÝ, Denis ŠUBERT, Daniel RENČIUK et. al.

Basic information

Original name

DNA i-motif formation at neutral pH is driven by kinetic partitioning

Authors

ŠKOLÁKOVÁ, Petra (203 Czech Republic), Martin GAJARSKÝ (703 Slovakia, belonging to the institution), Jan PALACKÝ, Denis ŠUBERT (703 Slovakia, belonging to the institution), Daniel RENČIUK (203 Czech Republic), Lukáš TRANTÍREK (203 Czech Republic, belonging to the institution), Jean-Louis MERGNY and Michaela VORLICKOVA (guarantor)

Edition

Nucleic Acids Research, Oxford University Press, 2023, 0305-1048

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 14.900 in 2022

RIV identification code

RIV/00216224:14740/23:00131413

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1093/nar/gkad119

UT WoS

000948336500001

Keywords in English

in-cell NMR; i-motif; DNA; kinetic partitioning

Abstract

V originále

Cytosine-rich DNA regions can form four-stranded structures based on hemi-protonated C.C+ pairs, called i-motifs (iMs). Using CD, UV absorption, NMR spectroscopy, and DSC calorimetry, we show that model (CnT3)3Cn (Cn) sequences adopt iM under neutral or slightly alkaline conditions for n > 3. However, the iMs are formed with long-lasting kinetics under these conditions and melt with significant hysteresis. Sequences with n > 6 melt in two or more separate steps, indicating the presence of different iM species, the proportion of which is dependent on temperature and incubation time. At ambient temperature, kinetically favored iMs of low stability are formed, most likely consisting of short C.C+ blocks. These species act as kinetic traps and prevent the assembly of thermodynamically favored, fully C.C+ paired iMs. A higher temperature is necessary to unfold the kinetic forms and enable their substitution by a slowly developing thermodynamic structure. This complicated kinetic partitioning process considerably slows down iM folding, making it much slower than the timeframes of biological reactions and, therefore, unlikely to have any biological relevance. Our data suggest kinetically driven iM species as more likely to be biologically relevant than thermodynamically most stable iM forms.

Links

EF18_046/0015974, research and development project

Name: Modernizace České infrastruktury pro integrativní strukturní biologii

GX19-26041X, research and development project

Name: Strukturní biologie nové generace: Od izolovaných molekul k buňkám, od buněk ke tkáním.

Investor: Czech Science Foundation

LM2018127, research and development project

Name: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

ŠKOLÁKOVÁ, Petra, Martin GAJARSKÝ, Jan PALACKÝ, Denis ŠUBERT, Daniel RENČIUK, Lukáš TRANTÍREK, Jean-Louis MERGNY and Michaela VORLICKOVA. DNA i-motif formation at neutral pH is driven by kinetic partitioning. Nucleic Acids Research. Oxford University Press, 2023, vol. 51, No 6, p. 2950-2962. ISSN 0305-1048. Available from: https://dx.doi.org/10.1093/nar/gkad119.

@article{2302402,
   author = {Školáková, Petra and Gajarský, Martin and Palacký, Jan and Šubert, Denis and Renčiuk, Daniel and Trantírek, Lukáš and Mergny, JeanandLouis and Vorlickova, Michaela},
   article_number = {6},
   doi = {http://dx.doi.org/10.1093/nar/gkad119},
   keywords = {in-cell NMR; i-motif; DNA; kinetic partitioning},
   language = {eng},
   issn = {0305-1048},
   journal = {Nucleic Acids Research},
   title = {DNA i-motif formation at neutral pH is driven by kinetic partitioning},
   url = {https://doi.org/10.1093/nar/gkad119},
   volume = {51},
   year = {2023}
}

TY  - JOUR
ID  - 2302402
AU  - Školáková, Petra - Gajarský, Martin - Palacký, Jan - Šubert, Denis - Renčiuk, Daniel - Trantírek, Lukáš - Mergny, Jean-Louis - Vorlickova, Michaela
PY  - 2023
TI  - DNA i-motif formation at neutral pH is driven by kinetic partitioning
JF  - Nucleic Acids Research
VL  - 51
IS  - 6
SP  - 2950-2962
EP  - 2950-2962
PB  - Oxford University Press
SN  - 03051048
KW  - in-cell NMR
KW  - i-motif
KW  - DNA
KW  - kinetic partitioning
UR  - https://doi.org/10.1093/nar/gkad119
N2  - Cytosine-rich DNA regions can form four-stranded structures based on hemi-protonated C.C+ pairs, called i-motifs (iMs). Using CD, UV absorption, NMR spectroscopy, and DSC calorimetry, we show that model (CnT3)3Cn (Cn) sequences adopt iM under neutral or slightly alkaline conditions for n > 3. However, the iMs are formed with long-lasting kinetics under these conditions and melt with significant hysteresis. Sequences with n > 6 melt in two or more separate steps, indicating the presence of different iM species, the proportion of which is dependent on temperature and incubation time. At ambient temperature, kinetically favored iMs of low stability are formed, most likely consisting of short C.C+ blocks. These species act as kinetic traps and prevent the assembly of thermodynamically favored, fully C.C+ paired iMs. A higher temperature is necessary to unfold the kinetic forms and enable their substitution by a slowly developing thermodynamic structure. This complicated kinetic partitioning process considerably slows down iM folding, making it much slower than the timeframes of biological reactions and, therefore, unlikely to have any biological relevance. Our data suggest kinetically driven iM species as more likely to be biologically relevant than thermodynamically most stable iM forms.
ER  -

ŠKOLÁKOVÁ, Petra, Martin GAJARSKÝ, Jan PALACKÝ, Denis ŠUBERT, Daniel RENČIUK, Lukáš TRANTÍREK, Jean-Louis MERGNY and Michaela VORLICKOVA. DNA i-motif formation at neutral pH is driven by kinetic partitioning. \textit{Nucleic Acids Research}. Oxford University Press, 2023, vol.~51, No~6, p.~2950-2962. ISSN~0305-1048. Available from: https://dx.doi.org/10.1093/nar/gkad119.

Detailed Information on Publication Record