1,6-Hexanediol Is Inducing Homologous Recombination by Releasing BLM from Assemblysomes in Drosophila melanogaster
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Tartalom: https://real.mtak.hu/188786/
Archívum: REAL
Gyűjtemény: Status = Published
Subject = Q Science / természettudomány: QD Chemistry / kémia
Subject = Q Science / természettudomány: Q1 Science (General) / természettudomány általában
Type = Article
Cím:
1,6-Hexanediol Is Inducing Homologous Recombination by Releasing BLM from Assemblysomes in Drosophila melanogaster
Létrehozó:
Gombás, Bence György
Villanyi, Zoltan
Dátum:
2024
Téma:
Q1 Science (General) / természettudomány általában
QD Chemistry / kémia
Tartalmi leírás:
We recently demonstrated that 1,6-hexanediol inhibits the formation of assemblysomes. These membraneless cell organelles have important roles in co-translational protein complex assembly and also store halfway translated DNA damage response proteins for a timely stress response. Recognizing the therapeutic potential of 1,6-hexanediol in dismantling assemblysomes likely to be involved in chemo- or radiotherapy resistance of tumor cells, we initiated an investigation into the properties of 1,6-hexanediol. Our particular interest was to determine if this compound induces DNA double-strand breaks by releasing the BLM helicase. Its yeast ortholog Sgs1 was confirmed to be a component of assemblysomes. The BLM helicase induces DNA damage when overexpressed due to the DNA double-strand breaks it generates during its normal function to repair DNA damage sites. It is evident that storing Sgs1 helicase in assemblysomes is crucial to express the full-length functional protein only in the event of DNA damage. Alternatively, if we dissolve assemblysomes using 1,6-hexanediol, ribosome-nascent chain complexes might become targets of ribosome quality control. We explored these possibilities and found, through the Drosophila wing-spot test assay, that 1,6-hexanediol induces DNA double-strand breaks. Lethality connected to recombination events following 1,6-hexanediol treatment can be mitigated by inducing DNA double-strand breaks with X-ray. Additionally, we confirmed that SMC5 recruits DmBLM to DNA damage sites, as knocking it down abolishes the rescue effect of DNA double-strand breaks on 1,6-hexanediol-induced lethality in Drosophila melanogaster.
Nyelv:
angol
Típus:
Article
PeerReviewed
info:eu-repo/semantics/article
Formátum:
text
Azonosító:
Gombás, Bence György and Villanyi, Zoltan (2024) 1,6-Hexanediol Is Inducing Homologous Recombination by Releasing BLM from Assemblysomes in Drosophila melanogaster. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 25 (3). pp. 1611-1622. ISSN 1661-6596
Kapcsolat:
MTMT:34540973 10.3390/ijms25031611
Létrehozó:
cc_by