J 2020

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

JURIKOVA, K., Martin GAJARSKÝ, M. HAJIKAZEMI, J. NOSEK, K. PROCHAZKOVA et. al.

Basic information

Original name

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

Authors

JURIKOVA, K., Martin GAJARSKÝ (703 Slovakia, belonging to the institution), M. HAJIKAZEMI, J. NOSEK, K. PROCHAZKOVA, K. PAESCHKE, Lukáš TRANTÍREK (203 Czech Republic, guarantor, belonging to the institution) and L. TOMASKA

Edition

Journal of Biological Chemistry, Bethesda, USA, Amer. Soc. Biochem. Mol. Biol. 2020, 0021-9258

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 5.157

RIV identification code

RIV/00216224:14740/20:00114648

Organization unit

Central European Institute of Technology

UT WoS

000550698000007

Keywords in English

telomere; telomerase; Saccharomyces cerevisiae; cell cycle; Cdc13; G-hairpin; G-quadruplex; folding kinetics

Tags

International impact, Reviewed
Změněno: 14/10/2024 15:51, Ing. Marie Švancarová

Abstract

V originále

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.

Links

GA17-12075S, research and development project
Name: Polymorfní G-quadruplexy v promotorových oblastech genů
Investor: Czech Science Foundation
LQ1601, research and development project
Name: CEITEC 2020 (Acronym: CEITEC2020)
Investor: Ministry of Education, Youth and Sports of the CR
NV19-08-00450, research and development project
Name: Atomárně rozlišená NMR spektroskopie in vivo jako nástroj pro biologické testování terapeuticky významných cílů v genomové ne-kanonické DNA a jejich interakcí s léčivy ve fenotypově diverzifikovaných nádorových buňkách.
Investor: Ministry of Health of the CR
90043, large research infrastructures
Name: CIISB