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.

Základní údaje

Originální název

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

Autoři

ŠKOLÁKOVÁ, Petra (203 Česká republika), Martin GAJARSKÝ (703 Slovensko, domácí), Jan PALACKÝ, Denis ŠUBERT (703 Slovensko, domácí), Daniel RENČIUK (203 Česká republika), Lukáš TRANTÍREK (203 Česká republika, domácí), Jean-Louis MERGNY a Michaela VORLICKOVA (garant)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 14.900 v roce 2022

Kód RIV

RIV/00216224:14740/23:00131413

Organizační jednotka

Středoevropský technologický institut

DOI

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

UT WoS

000948336500001

Klíčová slova anglicky

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

Štítky

CF NMR, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 6. 8. 2024 11:53, Mgr. Eva Dubská

Anotace

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.

Návaznosti

EF18_046/0015974, projekt VaV

Název: Modernizace České infrastruktury pro integrativní strukturní biologii

GX19-26041X, projekt VaV

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

Investor: Grantová agentura ČR, STRUCTURAL BIOLOGY – NEXT GENERATION: from isolated molecules to cells, from cells to tissues.

LM2018127, projekt VaV

Název: Česká infrastruktura pro integrativní strukturní biologii (Akronym: CIISB)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Czech Infrastructure for Integrative Structural Biology

Citovat

ŠKOLÁKOVÁ, Petra, Martin GAJARSKÝ, Jan PALACKÝ, Denis ŠUBERT, Daniel RENČIUK, Lukáš TRANTÍREK, Jean-Louis MERGNY a Michaela VORLICKOVA. DNA i-motif formation at neutral pH is driven by kinetic partitioning. Nucleic Acids Research. Oxford University Press, 2023, roč. 51, č. 6, s. 2950-2962. ISSN 0305-1048. Dostupné z: 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 a Michaela VORLICKOVA. DNA i-motif formation at neutral pH is driven by kinetic partitioning. \textit{Nucleic Acids Research}. Oxford University Press, 2023, roč.~51, č.~6, s.~2950-2962. ISSN~0305-1048. Dostupné z: https://dx.doi.org/10.1093/nar/gkad119.

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