Gergely Róna

Gergely Róna
NYU School of Medicine and Howard Hughes Medical Institute

PhD in Molecular Biology

About

83
Publications
5,958
Reads
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654
Citations
Introduction
I currently work at New York University School of Medicine and HHMI in the field of DNA Damage and Repair. As a molecular biologist, I am trying to gain a better understanding about the fundamental processes that maintain genomic integrity within our cells. I find it intriguing how information encoded in our genome is maintained with an unparalleled precision yet at the same time is plastic enough to be able to adopt to environmental changes.
Additional affiliations
September 2015 - April 2020
NYU School of Medicine and Howard Hughes Medical Institute
Position
  • PostDoc Position
Description
  • http://paganolab.org/index.html
September 2014 - December 2015
Budapest University of Technology and Economics
Position
  • Research Assistant
March 2014 - September 2014
NYU Cancer Institute, New York University School of Medicine and Howard Hughes Medical Institute
Position
  • Short term fellowship
Education
September 2010 - September 2013
Eötvös Lóránd University Faculty of Science, Biology Doctoral School
Field of study
  • Structural Biology Program
September 2005 - July 2010
Eötvös Lóránd University Faculty of Science
Field of study
  • Molecular Biology Faculty

Publications

Publications (83)
Article
Full-text available
The risk of zoonotic coronavirus spillover into the human population, as highlighted by the SARS-CoV-2 pandemic, demands the development of pan-coronavirus antivirals. The efficacy of existing antiviral ribonucleoside/ribonucleotide analogs, such as remdesivir, is decreased by the viral proofreading exonuclease NSP14-NSP10 complex. Here, using a no...
Article
Full-text available
Mammalian development, adult tissue homeostasis and the avoidance of severe diseases including cancer require a properly orchestrated cell cycle, as well as error-free genome maintenance. The key cell-fate decision to replicate the genome is controlled by two major signalling pathways that act in parallel—the MYC pathway and the cyclin D–cyclin-dep...
Article
Full-text available
D-type cyclins are central regulators of the cell division cycle and are among the most frequently deregulated therapeutic targets in human cancer¹, but the mechanisms that regulate their turnover are still being debated2,3. Here, by combining biochemical and genetics studies in somatic cells, we identify CRL4AMBRA1 (also known as CRL4DCAF3) as the...
Article
Full-text available
In order to understand the transmission and virulence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is necessary to understand the functions of each of the gene products encoded in the viral genome. One feature of the SARS-CoV-2 genome that is not present in related, common coronaviruses is ORF10, a putative 38-amino acid prot...
Article
Full-text available
DNA damage repair maintains the genetic integrity of cells in a highly reactive environment. Cells may accumulate various types of DNA damage due to both endogenous and exogenous sources such as metabolic activities or UV radiation. Without DNA repair, the cell's genetic code becomes compromised, undermining the structures and functions of proteins...
Article
Full-text available
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 treatments in human cancer cell...
Article
Full-text available
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 treatments in human cancer cell...
Article
Full-text available
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 treatments in human cancer cell...
Article
Full-text available
Background: The SMC5/6 complex, cohesin and condensin are the three mammalian members of the structural maintenance of chromosomes (SMC) family, large ring-like protein complexes that are essential for genome maintenance. The SMC5/6 complex is the least characterized complex in mammals; however, it is known to be involved in homologous recombinati...
Data
Raw, not cropped supporting Western blot files for: Rona, G., ... Pagano, M.: PARP1-dependent recruitment of the FBXL10-RNF68-RNF2 ubiquitin ligase to sites of DNA damage controls H2A.Z loading. Elife 7 (2018). DOI: http://dx.doi.org/10.17632/2k5jvkswvr.2#folder-d87d4fc5-dc24-4b66-9dc8-5914340a56b6
Preprint
Full-text available
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-...
Article
Diverse linkage in polyubiquitin chain structure gives cells an unparalleled complexity to virtually modulate all aspects of cell biology. Substrates can be covalently modified by ubiquitin chains of different topology. Proper DNA damage response takes advantage of this regulatory system and heavily relies on ubiquitin-based signaling. Moreover, in...
Article
Full-text available
Epithelial to mesenchymal transition (EMT) is a multipurpose process involved in wound healing, development, and certain pathological processes, such as metastasis formation. The Tks4 scaffold protein has been implicated in cancer progression; however, its role in oncogenesis is not well defined. In this study, the function of Tks4 was investigated...
Article
Full-text available
Sanitization of nucleotide pools is essential for genome maintenance. Deoxyuridine 5′-triphosphate nucleotidohydrolase (dUTPase) is a key enzyme in this pathway since it catalyzes the cleavage of 2′-deoxyuridine 5′-triphosphate (dUTP) into 2′-deoxyuridine 5′-monophosphate (dUMP) and inorganic pyrophosphate. Through its action dUTPase efficiently pr...
Article
Full-text available
The mammalian FBXL10-RNF68-RNF2 ubiquitin ligase complex (FRRUC) mono-ubiquitylates H2A at Lys119 to repress transcription in unstressed cells. We found that the FRRUC is rapidly and transiently recruited to sites of DNA damage in a PARP1- and TIMELESS-dependent manner to promote mono-ubiquitylation of H2A at Lys119, a local decrease of H2A levels,...
Data
Raw data for all graphs in main figures and figure supplements.
Article
Full-text available
Transmembrane proteins play crucial role in signaling, ion transport, nutrient uptake, as well as in maintaining the dynamic equilibrium between the internal and external environment of cells. Despite their important biological functions and abundance, less than 2% of all determined structures are transmembrane proteins. Given the persisting techni...
Article
Full-text available
SLBP (stem-loop binding protein) is a highly conserved factor necessary for the processing, translation, and degradation of H2AFX and canonical histone mRNAs. We identified the F-box protein cyclin F, a substrate recognition subunit of an SCF (Skp1-Cul1-F-box protein) complex, as the G2 ubiquitin ligase for SLBP. SLBP interacts with cyclin F via an...
Article
Proteins are translated in the cytoplasm, but many need to access the nucleus to perform their functions. Understanding how these nuclear proteins are transported through the nuclear envelope and how the import processes are regulated is therefore an important aspect of understanding cell function. Structural biology has played a key role in unders...
Article
Full-text available
The role of uracil in genomic DNA has been recently re-evaluated. It is now widely accepted to be a physiologically important DNA element in diverse systems from specific phages to antibody maturation and Drosophila development. Further relevant investigations would largely benefit from a novel reliable and fast method to gain quantitative and qual...
Article
dUTPase is a dNTP sanitizing enzyme that prevents the appearance of the potentially harmful uracil bases in DNA by hydrolyzing cellular dUTP. This function of dUTPase is found to be essential in many organisms including Drosophila melanogaster. Previously we showed that the expression pattern of dUTPase determines the extent of uracil accumulation...
Article
Full-text available
Nucleocytoplasmic trafficking of large macromolecules requires an active transport machinery. In many cases, this is initiated by binding of the nuclear localization signal (NLS) peptide of cargo proteins to importin- molecules. Fine orchestration of nucleocytoplasmic trafficking is of particularly high importance for proteins involved in maintenan...
Article
Full-text available
The authors respond to a comment by Alvisi & Jans [(2014), Acta Cryst. D70, 27752776] on the article Phosphorylation adjacent to the nuclear localization signal of human dUTPase abolishes nuclear import: structural and mechanistic insights[Rna et al. (2013), Acta Cryst. D69, 24952505].
Article
Full-text available
Transfer of phage-related pathogenicity islands of Staphylococcus aureus (SaPI-s) was recently reported to be activated by helper phage dUTPases. This is a novel function for dUTPases otherwise involved in preservation of genomic integrity by sanitizing the dNTP pool. Here we investigated the molecular mechanism of the dUTPase-induced gene expressi...
Article
Full-text available
Abstract Phosphorylation by the cyclin-dependent kinase 1 (Cdk1) adjacent to nuclear localization segments (NLSs) is an important mechanism of regulation of nucleocytoplasmic transport. However, no systematic survey has yet been performed in human cells to analyze this regulatory process, and the corresponding cell-cycle dynamics have not yet been...
Article
Genome integrity requires well controlled cellular pools of nucleotides. dUTPases are responsible for regulating cellular dUTP levels and providing dUMP for dTTP biosynthesis. In Staphylococcus , phage dUTPases are also suggested to be involved in a moonlighting function regulating the expression of pathogenicity-island genes. Staphylococcal phage...
Article
Phosphorylation adjacent to nuclear localization signals (NLSs) is involved in the regulation of nucleocytoplasmic transport. The nuclear isoform of human dUTPase, an enzyme that is essential for genomic integrity, has been shown to be phosphorylated on a serine residue (Ser11) in the vicinity of its nuclear localization signal; however, the effect...
Article
Full-text available
A thermophilic strain producing an extracellular esterase/lipase was isolated from a hot spring in Tăşnad, Romania, and was identified phenotypically and by 16S rDNA sequencing as Anoxybacillus flavithermus (GenBank ID: JQ267733). The gene encoding the putative carboxyl esterase (GenBank ID: JX494348) was cloned by direct PCR amplification from gen...
Article
Full-text available
Luminescent nanocrystals or quantum dots (QDs) have great potential for bioanalysis as well as optoelectronics. Here we report an effective and inexpensive fabrication method of silicon carbide quantum dots (SiC QDs), with diameter below 8 nm, based on electroless wet chemical etching. Our samples show strong violet-blue emission in the 410–450 nm...
Data
Full-text available
Percentage of fluorescent cells upon transfection with normal (T pl.) or uracil-substituted plasmids (U pl.). (A) Drosophila S2 cells, (B) HeLa cells. The number of observed fluorescent cells is also presented within the bars together with the total number of scored cells (shown in brackets). (PDF)
Data
Full-text available
Genomic position of UAS-IR constructs in dUTPase RNAi stocks. (PDF)
Data
Full-text available
dUTPase transgene rescues the dUTPase RNAi phenotype. Table shows the results of the rescue crosses. UAS-IR/SM6b; UAS-dUTPase-FLAG/TM3 males were crossed to Act-Gal4/CyO females (Figure S4). Two UAS-IR (21883 and 21884) and two transgenic rescue lines (DMDUT20 and DMDUT29) were combined. Number of progenies of the relevant F1 categories is shown. G...
Data
Full-text available
Scheme of crossing for silencing of dUTPase in Drosophila larvae and pupae and for rescue of dUTPase RNAi. Crossing schemes are shown on panel A and C: Act-Gal4 means Gal4 gene coupled with actin 5C promoter that result in ubiquitous and constitutive expression of yeast transcription factor, Gal4 in transgenic D. melanogaster driving transcription...
Data
Full-text available
Summary of pupal developmental processes. Red arrow shows the stage P5 (around 12–14 h after puparium formation) until lethality due to dUTPase silencing appear. (PDF)
Data
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Wild type structures of pharate adults 3 days after puparium formation. Wild type pupa was dissected at stage P11 where adult organs have already developed (A). Dissected Malpighian tubules (arrows on B) and Yellow Body (asterices on B) of wild type pupa these organs have never identified within dUTPase silenced pupae. (PDF)
Data
Full-text available
Uracil–DNA repair is perturbed in Drosophila. Microarray data available on FlyBase were used. Table shows mRNA level for genes involved in different DNA repair pathways, elements of uracil–DNA repair are highlighted on grey background. ↓ indicates mRNA level decrease, ↑ mRNA level increase, ≈ no stage-specific change. Note that the overall base exc...
Data
Supplementary information. Includes Supplementary Materials and Methods and Supplementary References. (DOC)
Data
Full-text available
Genomic uracil content of embryo is under detection limit. Uracil content of Drosophila embryonic genome compared to that of DNA plasmid purified from wild-type E. coli. Both of the samples showed a value under the detection limit. (PDF)
Data
Full-text available
Ung-ARP assay. UNG-ARP assay shows presence of uracil–DNA in Drosophila larvae. For negative and positive controls, genomic DNA samples from XL1 Blue and CJ236 ung-1, dut-1 E.coli strains were used respectively. CJ236 ung-1, dut-1 E.coli strain produces DNA with high uracil content (approx. 5500 uracil/million bases [8], [10]). (PDF)
Data