TY - JOUR AU - Tordai, Csongor AU - Hathy, Edit Margit AU - Gyergyák, Hella AU - Vincze, Katalin AU - Baradits, Máté AU - Koller, Júlia AU - Póti, Ádám AU - Jezsó, Bálint AU - Homolya, László AU - Molnár, Mária Judit AU - Nagy, László AU - Szüts, Dávid AU - Apáti, Ágota AU - Réthelyi, János TI - Probing the biological consequences of a previously undescribed de novo mutation of ZMYND11 in a schizophrenia patient by CRISPR genome editing and induced pluripotent stem cell based in vitro disease-modeling JF - SCHIZOPHRENIA RESEARCH J2 - SCHIZOPHR RES PY - 2024 SN - 0920-9964 DO - 10.1016/j.schres.2024.01.024 UR - https://m2.mtmt.hu/api/publication/34544485 ID - 34544485 LA - English DB - MTMT ER - TY - JOUR AU - Póti, Ádám AU - Szüts, Dávid AU - Vermezovic, Jelena TI - Mutational profile of the regenerative process and de novo genome assembly of the planarian Schmidtea polychroa JF - NUCLEIC ACIDS RESEARCH J2 - NUCLEIC ACIDS RES PY - 2024 SN - 0305-1048 DO - 10.1093/nar/gkad1250 UR - https://m2.mtmt.hu/api/publication/34487062 ID - 34487062 AB - Planarians are organisms with a unique capacity to regenerate any part of their body. New tissues are generated in a process that requires many swift cell divisions. How costly is this process to an animal in terms of mutational load remains unknown. Using whole genome sequencing, we defined the mutational profile of the process of regeneration in the planarian species Schmidtea polychroa. We assembled de novo the genome of S. polychroa and analyzed mutations in animals that have undergone regeneration. We observed a threefold increase in the number of mutations and an altered mutational spectrum. High allele frequencies of subclonal mutations in regenerated animals suggested that most of the cells in the regenerated animal were descendants of a small number of stem cells with high expansion potential. We provide, for the first time, the draft genome assembly of S. polychroa, an estimation of the germline mutation rate for a planarian species and the mutational spectrum of the regeneration process of a living organism. LA - English DB - MTMT ER - TY - JOUR AU - Fekete, Ferenc AU - Menus, Ádám AU - Tóth, Katalin AU - Kiss, Ádám Ferenc AU - Minus, Annamária AU - Sirok, Dávid AU - Belič, Aleš AU - Póti, Ádám AU - Csukly, Gábor AU - Monostory, Katalin TI - CYP1A2 expression rather than genotype is associated with olanzapine concentration in psychiatric patients JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 13 PY - 2023 IS - 1 PG - 13 SN - 2045-2322 DO - 10.1038/s41598-023-45752-6 UR - https://m2.mtmt.hu/api/publication/34256499 ID - 34256499 N1 - Institute of Enzymology, HUN-REN Research Centre for Natural Sciences, Magyar tudósok 2, Budapest, 1117, Hungary Doctoral School of Biology and Institute of Biology, Eötvös Loránd University, Pázmány Péter Sétány 1/A, Budapest, 1117, Hungary Department of Psychiatry and Psychotherapy, Semmelweis University, Balassa 6, Budapest, 1082, Hungary Toxi-Coop Toxicological Research Center, Magyar jakobinusok 4/B, Budapest, 1122, Hungary Lek Pharmaceuticals d.d., Kolodvorska 27, Menges, 1234, Slovenia Export Date: 09 November 2023; Cited By: 0; Correspondence Address: K. Monostory; Institute of Enzymology, HUN-REN Research Centre for Natural Sciences, Budapest, Magyar tudósok 2, 1117, Hungary; email: monostory.katalin@ttk.hu AB - Olanzapine is a commonly prescribed atypical antipsychotic agent for treatment of patients with schizophrenia and bipolar disorders. Previous in vitro studies using human liver microsomes identified CYP1A2 and CYP2D6 enzymes being responsible for CYP-mediated metabolism of olanzapine. The present work focused on the impact of CYP1A2 and CYP2D6 genetic polymorphisms as well as of CYP1A2 metabolizing capacity influenced by non-genetic factors (sex, age, smoking) on olanzapine blood concentration in patients with psychiatric disorders (N = 139). CYP2D6 genotype-based phenotype appeared to have negligible contribution to olanzapine metabolism, whereas a dominant role of CYP1A2 in olanzapine exposure was confirmed. However, CYP1A2 expression rather than CYP1A2 genetic variability was demonstrated to be associated with olanzapine concentration in patients. Significant contribution of − 163C > A (rs762551), the most common SNP (single nucleotide polymorphism) in CYP1A2 gene, to enhanced inducibility was confirmed by an increase in CYP1A2 mRNA expression in smokers carrying − 163A, and smoking was found to have appreciable impact on olanzapine concentration normalized by the dose/bodyweight. Furthermore, patients’ olanzapine exposure was in strong association with CYP1A2 expression; therefore, assaying CYP1A2 mRNA level in leukocytes can be an appropriate tool for the estimation of patients’ olanzapine metabolizing capacity and may be relevant in optimizing olanzapine dosage. LA - English DB - MTMT ER - TY - JOUR AU - Incze, Evelyn AU - Mangó, Katalin AU - Fekete, Ferenc AU - Kiss, Ádám Ferenc AU - Póti, Ádám AU - Harkó, T AU - Moldvay, Judit AU - Szüts, Dávid AU - Monostory, Katalin TI - Potential Association of Cytochrome P450 Copy Number Alteration in Tumour with Chemotherapy Resistance in Lung Adenocarcinoma Patients JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 17 PG - 16 SN - 1661-6596 DO - 10.3390/ijms241713380 UR - https://m2.mtmt.hu/api/publication/34117784 ID - 34117784 LA - English DB - MTMT ER - TY - JOUR AU - Gyüre, Zsolt Tamás AU - Póti, Ádám AU - Németh, Eszter AU - Szikriszt, Bernadett AU - Lózsa, Rita Bernadett AU - Krawczyk, Michał AU - Richardson, Andrea L. AU - Szüts, Dávid TI - Spontaneous mutagenesis in human cells is controlled by REV1-Polymerase ζ and PRIMPOL JF - CELL REPORTS J2 - CELL REP VL - 42 PY - 2023 IS - 8 PG - 18 SN - 2211-1247 DO - 10.1016/j.celrep.2023.112887 UR - https://m2.mtmt.hu/api/publication/34083629 ID - 34083629 N1 - Institute of Enzymology, Research Centre for Natural Sciences, Budapest, 1117, Hungary Doctoral School of Molecular Medicine, Semmelweis University, Budapest, 1085, Hungary Turbine Simulated Cell Technologies, Budapest, 1027, Hungary Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States National Laboratory for Drug Research and Development, Budapest, 1117, Hungary Cited By :2 Export Date: 17 January 2024 Correspondence Address: Richardson, A.L.; Johns Hopkins University School of MedicineUnited States; email: aricha58@jhu.edu Correspondence Address: Szüts, D.; Institute of Enzymology, Hungary; email: szuts.david@ttk.hu LA - English DB - MTMT ER - TY - THES AU - Póti, Ádám TI - A DNS-hibaelkerülés genomi lenyomatainak vizsgálata PY - 2022 SP - 136 UR - https://m2.mtmt.hu/api/publication/33614971 ID - 33614971 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Rachel, A. DeWeerd AU - Németh, Eszter AU - Póti, Ádám AU - Nataliya, Petryk AU - Chunlong, Chen AU - Olivier, Hyrien AU - Szüts, Dávid AU - Abby, Margaret Green TI - Prospectively-defined patterns of APOBEC3A mutagenesis are prevalent in human cancers JF - CELL REPORTS J2 - CELL REP VL - 38 PY - 2022 IS - 12 SN - 2211-1247 DO - 10.1016/j.celrep.2022.110555 UR - https://m2.mtmt.hu/api/publication/32730598 ID - 32730598 N1 - Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary Epigenetics & Cell Fate UMR7216, CNRS, University of Paris, 35 rue Hélène Brion, Paris, 75013, France Institut Curie, Université PSL, Sorbonne Université, CNRS UMR3244, Dynamics of Genetic Information, Paris, France Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, Université PSL, 46 rue d'Ulm, Paris, 75005, France Center for Genome Integrity, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, United States Export Date: 19 April 2022 Correspondence Address: Szüts, D.; Institute of Enzymology, Hungary; email: szuts.david@ttk.hu Correspondence Address: Green, A.M.; Department of Pediatrics, United States; email: abby.green@wustl.edu Funding details: K_134779, PD_134818, VEKOP-2.3.3-15-2017-00014 Funding details: National Institutes of Health, NIH, K08 CA212299 Funding details: U.S. Department of Defense, DOD, CA200867 Funding details: American Cancer Society, ACS Funding details: Cancer Research Foundation, CRF Funding details: Association pour la Recherche sur le Cancer, ARC Funding details: Children's Discovery Institute, CDI Funding details: Washington University School of Medicine in St. Louis, WUSM Funding details: Agence Nationale de la Recherche, ANR, 19-CE12-0016-02 Funding details: Fondation pour la Recherche Médicale, FRM, ANR-10-INBS-09, FRM DEI201512344404 Funding details: Ligue Contre le Cancer, 2010 BLAN 161501 Funding details: Centre National de la Recherche Scientifique, CNRS, 18CT014-00 Funding details: Institut National Du Cancer, INCa, PLBIO19-076 Funding text 1: The authors thank all members of the Green and Szüts labs for critical evaluation of experimental data and thoughtful review of the manuscript. We are thankful to colleagues and collaborators for experimental discussions and manuscript editing, especially Drs. Matthew Weitzman, Rahul Kohli, Sebastien Landry, Jeffrey Bednarski, and members of the Bednarski lab. We acknowledge the high-throughput sequencing facility of I2BC for its sequencing and bioinformatics expertise. BioRender was used to generate schematic figures and the graphical abstract. This work was supported by funding from the American Cancer Society (to A.M.G.), the Cancer Research Foundation (to A.M.G.), the National Institutes of Health ( K08 CA212299 to A.M.G.), the Department of Defense ( CA200867 to A.M.G.), the Children's Discovery Institute and the Washington University School of Medicine (to A.M.G.), and the National Research Development and Innovation Office of Hungary ( K_134779 and VEKOP-2.3.3-15-2017-00014 to D.S. and PD_134818 to E.N.). The C.-L.C. lab is supported by the YPI program of I. Curie, the ATIP-Avenir program from Centre National de la Recherche Scientifique and Plan Cancer ( N°18CT014-00 ), the Agence Nationale de la Recherche ( ReDeFINe 19-CE12-0016-02 ), and Institut National Du Cancer ( PLBIO19-076 ). The O.H. lab is supported by Ligue Nationale Contre le Cancer (Comité de Paris), Agence Nationale de la Recherche ( ANR 2010 BLAN 161501 ), Association pour la Recherche sur le Cancer , the Fondation pour la Recherche Médicale ( FRM DEI201512344404 ), and the France Génomique national infrastructure “Investissements d’Avenir” program managed by the ANR (ANR-10-INBS-09). LA - English DB - MTMT ER - TY - JOUR AU - Póti, Ádám AU - Szikriszt, Bernadett AU - Gervai, Judit Zsuzsanna AU - Chen, Dan AU - Szüts, Dávid TI - Characterisation of the spectrum and genetic dependence of collateral mutations induced by translesion DNA synthesis JF - PLOS GENETICS J2 - PLOS GENET VL - 18 PY - 2022 IS - 2 SN - 1553-7390 DO - 10.1371/journal.pgen.1010051 UR - https://m2.mtmt.hu/api/publication/32679015 ID - 32679015 N1 - Export Date: 30 March 2022 Correspondence Address: Szüts, D.; Institute of Enzymology, Hungary; email: szuts.david@ttk.hu Funding details: FIEK_16-1-2016-0005, K_134779, PD_121381, VEKOP-2.3.3-15-2017-00014 Funding details: Magyar Tudományos Akadémia, MTA, LP2011-015 Funding text 1: This work was supported by the Hungarian Academy of Sciences (https://mta.hu) [Momentum Grant LP2011-015 to DS] and the National Research, Technology and Innovation Fund of Hungary (https://nkfih.gov.hu) [K_124881, K_134779, FIEK_16-1-2016-0005 and VEKOP-2.3.3-15-2017-00014 to DS, PD_121381 to BS and DS]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. LA - English DB - MTMT ER - TY - JOUR AU - Chen, Dan AU - Gervai, Judit Zsuzsanna AU - Póti, Ádám AU - Németh, Eszter AU - Szeltner, Zoltán AU - Szikriszt, Bernadett AU - Gyüre, Zsolt Tamás AU - Zámborszky, Judit AU - Ceccon, Marta AU - d’Adda di Fagagna, Fabrizio AU - Szállási, Zoltán AU - Richardson, Andrea L. AU - Szüts, Dávid TI - BRCA1 deficiency specific base substitution mutagenesis is dependent on translesion synthesis and regulated by 53BP1 JF - NATURE COMMUNICATIONS J2 - NAT COMMUN VL - 13 PY - 2022 IS - 1 PG - 13 SN - 2041-1723 DO - 10.1038/s41467-021-27872-7 UR - https://m2.mtmt.hu/api/publication/32586615 ID - 32586615 N1 - These authors contributed equally: Dan Chen, Judit Z. Gervai. LA - English DB - MTMT ER - TY - JOUR AU - Pavani, M. AU - Bonaiuti, P. AU - Chiroli, E. AU - Gross, F. AU - Natali, F. AU - Macaluso, F. AU - Póti, Ádám AU - Pasqualato, S. AU - Farkas, Zoltán AU - Pompei, S. AU - Cosentino, Lagomarsino M. AU - Rancati, G. AU - Szüts, Dávid AU - Ciliberto, Andrea TI - Epistasis, aneuploidy, and functional mutations underlie evolution of resistance to induced microtubule depolymerization JF - EMBO JOURNAL J2 - EMBO J VL - 40 PY - 2021 IS - 22 SN - 0261-4189 DO - 10.15252/embj.2021108225 UR - https://m2.mtmt.hu/api/publication/32341173 ID - 32341173 N1 - Funding details: AIRC‐IG 23258, UNKP‐20‐5‐SZTE‐646, UNKP‐21‐5‐SZTE‐562 Funding details: FIEK_16‐1‐2016‐0005, K_124881, NRF‐NRFI05‐2019‐0008 Funding details: Ministero della Salute Funding details: Magyar Tudományos Akadémia, MTA, BO/779/20 Funding details: Fondazione Umberto Veronesi Funding details: Associazione Italiana per la Ricerca sul Cancro, AIRC, AIRC‐IG 21556 Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, FK 128775 Funding text 1: This paper is dedicated to John J. Tyson, mentor and friend, on the occasion of his retirement. We thank Silke Hauf, Claudio Vernieri, and Andrea Musacchio for constructive comments on the manuscript. Camilla Cancrini helped us in the final stages of this work. We thank Marco Foiani, Michael Knop, Roberta Fraschini, Simonetta Piatti, and Tim Huffaker for sharing reagents with us. Work in the group of AC is financed by AIRC, the Italian association for cancer research (Grant AIRC‐IG 21556); MP benefits of a AIRC fellowship; SeP receives supports from the Italian Ministry of Health (Ricerca Corrente and 5x1000 funds); SiP benefits from a Fondazione Umberto Veronesi fellowship; ZF is supported by the National Research, Development and Innovation Office of Hungary (FK 128775), a Janos Bolyai Research Fellowship from the Hungarian Academy of Sciences (BO/779/20) and the New National Excellence Program of the Hungarian Ministry of Human Capacities (Bolyai+, UNKP‐20‐5‐SZTE‐646 and UNKP‐21‐5‐SZTE‐562); the group of MCL is supported by AIRC, the Italian association for cancer research (Grant AIRC‐IG 23258); DS lab is supported by the National Research, Development and Innovation Fund of Hungary (grants K_124881 and FIEK_16‐1‐2016‐0005); GR lab is supported by a Singapore NRF Investigatorship (NRF‐NRFI05‐2019‐0008); the Hungarian Academy of Sciences sponsored the collaboration between the groups of AC and DS by awarding a visiting fellowship to AC. AB - Cells with blocked microtubule polymerization are delayed in mitosis, but eventually manage to proliferate despite substantial chromosome missegregation. While several studies have analyzed the first cell division after microtubule depolymerization, we have asked how cells cope long-term with microtubule impairment. We allowed 24 clonal populations of yeast cells with beta-tubulin mutations preventing proper microtubule polymerization, to evolve for ˜150 generations. At the end of the laboratory evolution experiment, cells had regained the ability to form microtubules and were less sensitive to microtubule-depolymerizing drugs. Whole-genome sequencing identified recurrently mutated genes, in particular for tubulins and kinesins, as well as pervasive duplication of chromosome VIII. Recreating these mutations and chromosome VIII disomy prior to evolution confirmed that they allow cells to compensate for the original mutation in beta-tubulin. Most of the identified mutations did not abolish function, but rather restored microtubule functionality. Analysis of the temporal order of resistance development in independent populations repeatedly revealed the same series of events: disomy of chromosome VIII followed by a single additional adaptive mutation in either tubulins or kinesins. Since tubulins are highly conserved among eukaryotes, our results have implications for understanding resistance to microtubule-targeting drugs widely used in cancer therapy. © 2021 IFOM – the FIRC Institute of Molecular Oncology LA - English DB - MTMT ER -