Role of folding kinetics of secondary structures in telomeric G-overhangs in the regulation of telomere maintenance inSaccharomyces cerevisiae

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F20%3A00539336" target="_blank" >RIV/68081707:_____/20:00539336 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14740/20:00114648

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0021925817503208?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0021925817503208?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1074/jbc.RA120.012914" target="_blank" >10.1074/jbc.RA120.012914</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Role of folding kinetics of secondary structures in telomeric G-overhangs in the regulation of telomere maintenance inSaccharomyces cerevisiae

Popis výsledku v původním jazyce

The ends of eukaryotic chromosomes typically contain a 3? ssDNA G-rich protrusion (G-overhang). This overhang must be protected against detrimental activities of nucleases and of the DNA damage response machinery and participates in the regulation of telomerase, a ribonucleoprotein complex that maintains telomere integrity. These functions are mediated by DNA-binding proteins, such as Cdc13 inSaccharomyces cerevisiae, and the propensity of G-rich sequences to form various non-B DNA structures. Using CD and NMR spectroscopies, we show here that G-overhangs ofS. cerevisiaeform distinct Hoogsteen pairing?based secondary structures, depending on their length. Whereas short telomeric oligonucleotides form a G-hairpin, their longer counterparts form parallel and/or antiparallel G-quadruplexes (G4s). Regardless of their topologies, non-B DNA structures exhibited impaired binding to Cdc13in vitroas demonstrated by electrophoretic mobility shift assays. Importantly, whereas G4 structures formed relatively quickly, G-hairpins folded extremely slowly, indicating that short G-overhangs, which are typical for most of the cell cycle, are present predominantly as single-stranded oligonucleotides and are suitable substrates for Cdc13. Using ChIP, we show that the occurrence of G4 structures peaks at the late S phase, thus correlating with the accumulation of long G-overhangs. We present a model of how time- and length-dependent formation of non-B DNA structures at chromosomal termini participates in telomere maintenance.

Název v anglickém jazyce

Role of folding kinetics of secondary structures in telomeric G-overhangs in the regulation of telomere maintenance inSaccharomyces cerevisiae

Popis výsledku anglicky

The ends of eukaryotic chromosomes typically contain a 3? ssDNA G-rich protrusion (G-overhang). This overhang must be protected against detrimental activities of nucleases and of the DNA damage response machinery and participates in the regulation of telomerase, a ribonucleoprotein complex that maintains telomere integrity. These functions are mediated by DNA-binding proteins, such as Cdc13 inSaccharomyces cerevisiae, and the propensity of G-rich sequences to form various non-B DNA structures. Using CD and NMR spectroscopies, we show here that G-overhangs ofS. cerevisiaeform distinct Hoogsteen pairing?based secondary structures, depending on their length. Whereas short telomeric oligonucleotides form a G-hairpin, their longer counterparts form parallel and/or antiparallel G-quadruplexes (G4s). Regardless of their topologies, non-B DNA structures exhibited impaired binding to Cdc13in vitroas demonstrated by electrophoretic mobility shift assays. Importantly, whereas G4 structures formed relatively quickly, G-hairpins folded extremely slowly, indicating that short G-overhangs, which are typical for most of the cell cycle, are present predominantly as single-stranded oligonucleotides and are suitable substrates for Cdc13. Using ChIP, we show that the occurrence of G4 structures peaks at the late S phase, thus correlating with the accumulation of long G-overhangs. We present a model of how time- and length-dependent formation of non-B DNA structures at chromosomal termini participates in telomere maintenance.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

Journal of Biological Chemistry

ISSN

0021-9258

e-ISSN

—

Svazek periodika

295

Číslo periodika v rámci svazku

27

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

8958-8971

Kód UT WoS článku

000550698000007

EID výsledku v databázi Scopus

2-s2.0-85087532995