Emetine blocks DNA replication via proteosynthesis inhibition not by targeting Okazaki fragments
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F22%3A73614432" target="_blank" >RIV/61989592:15110/22:73614432 - isvavai.cz</a>
Výsledek na webu
<a href="https://www.life-science-alliance.org/content/5/12/e202201560" target="_blank" >https://www.life-science-alliance.org/content/5/12/e202201560</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.26508/lsa.202201560" target="_blank" >10.26508/lsa.202201560</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Emetine blocks DNA replication via proteosynthesis inhibition not by targeting Okazaki fragments
Popis výsledku v původním jazyce
DNA synthesis of the leading and lagging strands works independently and cells tolerate single-stranded DNA generated during strand uncoupling if it is protected by RPA molecules. Natural alkaloid emetine is used as a specific inhibitor of lagging strand synthesis, uncoupling leading and lagging strand replication. Here, by analysis of lagging strand synthesis inhibitors, we show that despite emetine completely inhibiting DNA replication: it does not induce the generation of single-stranded DNA and chromatin-bound RPA32 (CB-RPA32). In line with this, emetine does not activate the replication checkpoint nor DNA damage response. Emetine is also an inhibitor of proteosynthesis and ongoing proteosynthesis is essential for the accurate replication of DNA. Mechanistically, we demonstrate that the acute block of proteosynthesis by emetine temporally precedes its effects on DNA replication. Thus, our results are consistent with the hypothesis that emetine affects DNA replication by proteosynthesis inhibition. Emetine and mild POLA1 inhibition prevent S-phase poly(ADP-ribosyl)ation. Collectively, our study reveals that emetine is not a specific lagging strand synthesis inhibitor with implications for its use in molecular biology.
Název v anglickém jazyce
Emetine blocks DNA replication via proteosynthesis inhibition not by targeting Okazaki fragments
Popis výsledku anglicky
DNA synthesis of the leading and lagging strands works independently and cells tolerate single-stranded DNA generated during strand uncoupling if it is protected by RPA molecules. Natural alkaloid emetine is used as a specific inhibitor of lagging strand synthesis, uncoupling leading and lagging strand replication. Here, by analysis of lagging strand synthesis inhibitors, we show that despite emetine completely inhibiting DNA replication: it does not induce the generation of single-stranded DNA and chromatin-bound RPA32 (CB-RPA32). In line with this, emetine does not activate the replication checkpoint nor DNA damage response. Emetine is also an inhibitor of proteosynthesis and ongoing proteosynthesis is essential for the accurate replication of DNA. Mechanistically, we demonstrate that the acute block of proteosynthesis by emetine temporally precedes its effects on DNA replication. Thus, our results are consistent with the hypothesis that emetine affects DNA replication by proteosynthesis inhibition. Emetine and mild POLA1 inhibition prevent S-phase poly(ADP-ribosyl)ation. Collectively, our study reveals that emetine is not a specific lagging strand synthesis inhibitor with implications for its use in molecular biology.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10620 - Other biological topics
Návaznosti výsledku
Projekt
Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Ostatní
Rok uplatnění
2022
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Life Science Alliance
ISSN
2575-1077
e-ISSN
2575-1077
Svazek periodika
5
Číslo periodika v rámci svazku
12
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
10
Strana od-do
"e202201560"
Kód UT WoS článku
000858965900002
EID výsledku v databázi Scopus
2-s2.0-85140415949