Biology subjects

Vertessy, B. G.

Publications and source records attributed to Vertessy, B. G..

3 recordsLinked to original sources

bioRxiv2026

Recognizing dUTPase as a mitotic factor essential for early embryonic development

dUTPase is universally regarded as a metabolic sanitizing enzyme that protects genomes by preventing the incorporation of uracil into DNA. Despite its essentiality across eukaryotes, no function beyond nucleotide sanitization has been demonstrated. Here, we uncover a conserved, non-canonical role for dUTPase as a regulator of mitosis. Using Drosophila and mouse models, we demonstrate that dUTPase loss causes early embryonic lethality characterized by severe mitotic failure that, cannot be rescued by disabling uracil-DNA repair, uncoupling dUTPase essentiality from DNA repair pathways. Mechanistically, dUTPase dynamically associates with the mitotic spindle and centrosomes, and its depletion induces centrosome amplification and chromosome segregation defects. Beyond cell division, dUTPase dosage bidirectionally controls cell migration, linking its mitotic function to cellular behaviors relevant for metastasis. Together, our findings redefine dUTPase as a moonlighting mitotic factor that coordinates centrosome integrity and spindle dynamics, expanding its known repertoire beyond nucleotide metabolism. HighlightsdUTPase deficiency leads to mitotic defects during early embryonic development in both Drosophila and mouse models dUTPase shows dynamic spatiotemporal localization associated with microtubules through mitosis dUTPase is essential for the normal number and intracellular localization of centrosomes dUTPase deficiency counteracts while its overexpression enhances cell migration

molecular biology↗

bioRxiv2020

Dissection of Plasmodium falciparum developmental stages with multiple imaging methods

Efficient malaria treatment is a global challenge, requiring in-depth view into the maturation of malaria parasites during the intraerythrocytic cycle. Exploring structural and functional variations of the parasites through the intraerythrocytic stages and their impact on red blood cell (RBCs) is a cornerstone of antimalarial drug development. In order to trace such changes in fine steps of parasite development, we performed an imaging study of RBCs infected by Plasmodium falciparum, using atomic force microscopy (AFM) and total internal reflection fluorescence microscopy (TIRF), further supplemented with bright field microscopy for the direct assignment of the stages. This multifaceted imaging approach allows to reveal structure-functionality relations via correlations of the parasite maturation with morphological and fluorescence properties of the stages. We established identification patterns characteristic to the different parasite stages based on the height profile of infected RBCs, as obtained by AFM, which show close correlation with typical fluorescence (TIRF) maps of RBCs. Furthermore, we found that hemozoin crystals exhibit a strong optical contrast by quenching fluorescence. We demonstrate that these topographic and optical features also provide a tool to locate the hemozoin crystals within the RBCs and, in turn, to follow their growth.

biophysics↗

bioRxiv2020

Genome-wide alterations of uracil distribution patterns in human DNA upon chemotherapeutic treatments

Numerous anti-cancer drugs perturb thymidylate biosynthesis and lead to genomic uracil incorporation contributing to their antiproliferative effect. Still, it is not yet characterized if uracil incorporations have any positional preference. Here, we aimed to uncover genome-wide alterations in uracil pattern upon drug-treatment in human cancer cell-line HCT116. We developed a straightforward U-DNA sequencing method (U-DNA-Seq) that was combined with in situ super-resolution imaging. Using a novel robust analysis pipeline, we found broad regions with elevated probability of uracil occurrence both in treated and non-treated cells. Correlation with chromatin markers and other genomic features shows that non-treated cells possess uracil in the late replicating constitutive heterochromatic regions, while drug treatment induced a shift of incorporated uracil towards more active/functional segments. Data were corroborated by colocalization studies via dSTORM microscopy. This approach can also be applied to study the dynamic spatio-temporal nature of genomic uracil.

biochemistry↗