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Adenosine (de)methylation on the crossroads of RNA and DNA synthesis

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KRISHNA Shwetha OBRDLÍK Aleš RENGARAJ Praveenkumar ŠEMBEROVÁ RÁJECKÁ Veronika ZUEV Anton PESCHELOVÁ Helena KOZLOVÁ Veronika ŠMÍDA Michal POTĚŠIL David DOBROVOLNÁ Jana VAŇÁČOVÁ Štěpánka

Rok publikování 2025
Druh Konferenční abstrakty
Fakulta / Pracoviště MU

Středoevropský technologický institut

Citace
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Popis Eukaryotic mRNAs are subject to significant chemical modifications that exhibit a multi-layered regulation of transcript metabolism. Among these, N6-methyladenosine (m6A) and N6-2’O-dimethyladenosine (m6Am) are two prevalent modifications in higher eukaryotes. The dynamics of these modifications are tightly governed by dedicated machineries, the perturbation of which destabilise cellular homeostasis. In a recent study using proximity-based labelling approach, we identified that m6A/m eraser protein – FTO – was proximally interacting with proteins in DNA replication and repair pathways. To elucidate this further, in this study we performed subsequent protein interaction assays and genome wide CRISPR screening, where we identified multiple candidates involved at different levels of DNA synthesis. Additionally, we performed functional assays to further investigate the relevance of FTO in these processes. Preliminary results from these functional assays positively correlate with our observations from the high throughput screening approaches, highlighting the importance of the m6A/m modifying enzyme, FTO, in the maintenance of genome integrity.

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