DNA damage group at Croatian Television, 30 October, 2024
Marta has been invited to give a 10-minute interview about our research in the studio at the show ‘'Prometheus - Signature Science''. The show is available at the following link: https://www.youtube.com/watch?v=S0aeA3GJc5I, 10. - 20. minute
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Our collaborative study with Ramadan group from Oxford University and Nanyang Technological University in Singapur is published in Cell!
September 2024
The research project led by Pauline Lescaux and Kristijan Ramadan (https://www.imm.ox.ac.uk/research/research-groups/ramadan-group-1) led to the discovery of a new mechanism of DNA repair, nucleophagy. We have shown that the repair of DNA-protein crosslinks (DPCs) which is initiated in the nucleus by the adaptor protein TEX264 and the ATPase segregase p97, is completed in the lysosomes. We show that DPCs are extruded through the nuclear envelope and taken up by the lysosome through the process of TEX264-mediated signaling. The repair pathway is dissected in vitro and in cultured cells, and we also show that it is relevant at the organismal level using zebrafish animal model. Additionally, we show that our findings are relevant for the chemotherapy protocols in colorectal cancer patients. Official press releases as well as articles published in local newspapers are available at the following links:
https://www.ox.ac.uk/news/2024-09-13-study-discovers-new-process-cells-repair-dna-damage
https://www.ntu.edu.sg/news/detail/study-discovers-new-process-for-cells-to-repair-dna-damage
https://theindependent.sg/ntu-oxford-team-uncovers-new-process-for-cells-to-repair-dna-damage/
Link to access the original article: https://www.sciencedirect.com/science/article/pii/S0092867424009115
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Our new paper on the role of Tyrosyl-DNA phosphodiesterase 2 (Tdp2) in DPC repair is out!
August, 2024
We have shown that silencing of TDP2 in zebrafish embryos causes accumulation of DNA-protein crosslinks and leads to the accumulation of double strand breaks. We found that Ku80-DPCs are removed by TDP2, whereas histone H3-DPCs are not. In addition, we have found that in vivo, TDP1 and TDP2 cannot compensate for each other, as overexpression of Tdp2 does not result in the cleavage of a Tdp1 substrate in embryos. Our results contribute to a more comprehensive understanding of DPC repair at the organismal level and underscore the significance of TDP2 in maintaining genome stability.
DNA damage group at Croatian Television
9 May, 2024
The TV show Prometheus presents new scientific discoveries every week. Our group was featured in a 5-minute video in which Ivan, Cecile, Marin and Marta were in the lab explaining how they work with cells and zebrafish. The methods we use were explained for the general public, including CRISPR/Cas-mediated gene editing in zebrafish and basic concepts of DNA-protein crosslink repair. In addition, new discoveries on the interplay of SPRTN protease and TDP1 in DPC repair in human cells and zebrafish embryos, published in Open Biology were explained to the public. The show is available at: https://www.youtube.com/watch?v=IzK_OEKWiBk&list=PLuEWODEWd3kOY-AhAL7LLe3crhWNlj4eS&index=11, 4. - 9. minute
Marta gives an invited talk at the FEBS conference in Milan.
July, 2024
The 48th FEBS congress - Mining biochemistry for human health and well-being had over 1,500 attendees from all over the world. The session on gene editing was packed with more than 200 scientists in the audience. The talk titled ‘’Deciphering DNA-protein crosslink repair in vivo using CRISPR/Cas genome editing in a zebrafish model''.
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Pre-Christmas lab dinner at Garden Brewery, Zagreb
December 2023, Zagreb
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DNA damage group at the MUZZA Science Week
12-14 April, 2024
The Science Week was organized by the NGO MUZZA and University of Zagreb and included three days of exhibitions, workshops, experiments and lectures (https://muzza.hr/tjedan-znanosti-2024/) from 10 am to 7 pm at the Rectorate of the University of Zagreb (SEECEL building).
DNA damage group presented the scientific work with the zebrafish animal model and its application in biology and medicine. Over 300 participants from primary and secondary schools visited our interactive exhibition, which was open throughout the Science Week and where ten scientists, MSc and PhD students presented the experiments. We showed live vertebrate embryogenesis, CRISPR-Cas genome editing and monitoring of DNA repair in embryos with the equipment we have temporarily set up for MUZZA (microscopes, incubator, aquaria).
Ivan defends his PhD thesis
November 2023, Zagreb
Ivan has successfully defended his thesis ‘’The repair of Topoisomerase 1 and 2 DNA-protein crosslinks in vivo’’. After four years of research, Ivan has completed his doctoral thesis which was funded by the HRZZ Installation grant in Marta Popovic’s lab. He worked intensively on the repair of the two most common enzymatic DPCs, topoisomerase 1 and 2 in cell and zebrafish models. Ivan has established many new methods in the lab, including CRISPR-Cas mediated gene editing in zebrafish, DPC isolation protocols from zebrafish embryos, measurement of enzymatic TDP activity, detection of specific DPCs in embryonic tissues and much more. His first article was been recently published in the journal Open biology, while more articles will come out in 2024. Ivan obtained a postdoctoral position in the group, where he continues his research on DPC repair in vivo.
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First paper from the DPC group published in Open Biology! Check out our recent paper on DNA-protein crosslink repair (DPCR) including the first animal model created at Ruder Boskovic Institute, Tdp1-deficient zebrafish strain!
Tyrosyl-DNA phosphodiesterase 1 (TDP1) and SPRTN protease repair histone 3 and topoisomerase 1 DNA–protein crosslinks in vivo, October 4th, 2023
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https://royalsocietypublishing.org/doi/10.1098/rsob.230113
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Our publication has been featured at the Institute’s website and social networks:
​https://www.irb.hr/Novosti/Znacajan-napredak-u-razumijevanju-popravka-DNA
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Using the zebrafish animal model and human RPE1 cells, we demonstrate that SPRTN protease and Tyrosyl DNA phosphodiesterase 1 (TDP1) repair endogenous, camptothecin and formaldehyde-induced DPCs. Main conclusions from the paper are:
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Beyond its recognized role in the repair of Topoisomerase 1 (TOP1)-DPCs, Tdp1 is important for the resolution of H3-DPCs in vivo and in cell models, and potentially for other 3' end-trapped DPCs.
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SPRTN protease is responsible for the repair of a broad spectrum of DPCs, TOP1- and H3-DPCs, both in vivo and in cell models.
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TDP1 and SPRTN act in different DPCR pathways for the resolution of endogenous DPCs, including TOP1- DPCs. However, they act epistatically to resolve endogenous H3-DPCs, both in vivo and in cell models.
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Following DPC induction by camptothecin and formaldehyde, TDP1 and SPRTN act epistatically in the repair of total, TOP1-, and H3-DPCs, both in vivo and in cell models.
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When comparing two systems used to study DPCR: human RPE1 cells and zebrafish embryos, we observed similar patterns of DPC dynamics, both after gene disruption and after exposure to .
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The novel role of TDP1 in the repair of cellular DPCs and histone-DPCs should be considered for its implications for the development of cancer therapies. Combination therapy targeting SPRTN and TDP1 could be a promising strategy to treat cancers along with irinotecan and topotecan which are already used in clinics to treat ovarian, colorectal, and recurrent small cell lung cancer.
3rd Chromosomal Instability as a Driver of Human Disease Conference
October 2023, Dubrovnik, Croatia
Great conference in the field of DNA damage and repair! We presented our recent work on DNA-protein crosslink repair (DPCR) including characterization of SPRTN and ACRC proteases, tyrosyl-DNA phosphodiesterases and p97 ATPase. We showed the results obtained from new animal models we have developed to study DNA-protein crosslink repair (DPCR) using CRISPR-Cas gene editing in zebrafish.
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EMBO poster prize
October 2023, Dubrovnik, Croatia
Ivan was awarded the prize for the best poster by EMBO at the 3rd Chromosomal Instability as a Driver of Human Disease Conference! He was selected by the EMBO representative from 65 posters presented at the conference.
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Exciting news! ACRC is an essential DPC protease in vertebrates
February, 2023
Our insights into ACRC protease show that it is essential for vertebrate development where it repairs DNA-protein crosslinks including histone-DPCs. You can access the pre-print at: https://www.biorxiv.org/content/10.1101/2023.03.07.531502v1.
New discoveries: TDP1 and SPRTN repair histone H3 and topoisomerase 1 DPCs
February, 2023
Exciting news! Our latest data reveal new mechanism of DNA-protein crosslink repair in vivo, shedding new light on understanding DPC-related diseases and identifying potential chemotherapeutic targets. Check our pre-print 'Tyrosyl-DNA phosphodiesterase 1 (TDP1) and SPRTN protease repair histone 3 and topoisomerase 1 DNA-protein crosslinks in vivo’ at: https://www.biorxiv.org/content/10.1101/2023.03.01.530659v1.
Christine defends her PhD thesis
February, 2023
Our first PhD student, Christine Supina-Pavić defended the PhD thesis last month. Christine investigated the role of ACRC protease and NER pathway in the repair of DNA-protein crosslinks in zebrafish.
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Master students defend their theses
February, 2023
Master student Tea Bezjak successfully defended her MSc thesis last month. Tea spent a year in our lab working on protein purification of SPRTN and p97 and biochemical characterization of their interaction. Chemistry programme, Faculty of Sciences, University of Zagreb.
Master student Luka Vinković defended his thesis on expression analysis of DNA-protein crosslink repair factors in ageing zebrafish. Molecular Biology Programme, Faculty of Sciences, University of Zagreb.
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HDBMB22 conference in Brela, Croatia
September, 2022
Marta is a board member and member of the organizing committee for the biannual international conference of the Croatian society of Biochemistry and Molecular Biology (HDBMB). We had 220 participants from the EU: great venue, great lectures:)! We won the science quiz night (team ‘’Danio’’). Ivan received the best poster award for his work on the role of Tdp2 in DPC repair during zebrafish embryonic development!
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Vedrana defends her MSc theses
September, 2022
MSc student Vedrana Vukasovic Loncar successfully defended her theses within the graduate MSc programme Molecular Biotechnology at the University of Zagreb. Vedrana was with us for one year under the supervision of Dr. sc. Nives Ivic and worked on the biochemical characterization of the interaction of SPRTN and p97.
Arturo Falaschi Conference ‘At the intersection of DNA Replication and genome maintenance: from mechanisms to therapy’, Trieste, Italy.
July 2022
Ivan, Cecile, Nives and Marta presented DPC repair results from both projects: bilateral Slovenian-Croatian grant ‘’Structural characterization of DPC factors’’ and HRZZ Installation grant ‘’Deciphering DPCR in zebrafish’’. Marta gave a talk on our recent characterization of a DPC protease: ‘’DNA protein crosslink repair protease in embryonic development’’.
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IUBMB/FEBS/PABMB ‘The Biochemistry global summit’, Lisbon, Portugal
July 2022
IUBMB/FEBS/PABMB ‘The Biochemistry global summit’, Lisbon, Portugal
Marta, Cecile and Ivan presented their recent work on DPC repair, finally live! Ivan received a FEBS student fellowship to attend the conference.
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March, 2022
MSc student Vanna Medved successfully defended her theses within the MSc programme in Molecular Biotechnology at the University of Zagreb. Vanna stayed in our lab at Ruder Boskovic Institute for one year and worked on the analysis of tissue expression of factors involved in DPC repair.
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PhD student Marin Kutnjak joins the lab to work on Slovenian-Croatian Bilateral Project 'Structural characterization of factors involved in DNA-protein crosslink repair'
December, 2021.
Master students Matea Eršetić and Marin Kutnjak (Molecular Biology programme) successfully defended their theses at the Faculty of Sciences, University of Zagreb.
September, 2021.
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Grant awarded to the PI for 4 years PhD student position by the Croatian National Science Foundation
April, 2021
dr. Popovic was invited to give a comment on this year’s Nobel Prize for Chemistry for the discovery of genetic scissors on Croatian radio 1 radio show ‘I love Platon’ at https://radio.hrt.hr/aod/drag-mi-je-platon/356904/.
October 9, 2020
Project grant awarded to dr. Popovic in collaboration with dr. Ivic at Ruder Boskovic Institute in Zagreb and dr. Podobnik at the Chemistry Institute in Ljubljana (SLO) (Slovenian – Croatian bilateral research project (IPS-2020-01, 4225) in October, 2020.
October, 2020
Two master students join the group for 2020/2021, Matea Ersetic and Marin Kutnjak from Molecular Biology programme at the Faculty of Science at the University of Zagreb in September, 2020.
September, 2020
Two master students, Luka Jukic and Valentin Dakic, from Biochemistry programme at the Faculty of Science at the University of Zagreb successfully completed their one-year lab work on DPC protein repair and are defending their theses in December, 2020.
September, 2020
Two diploma students, Lucija Mance and Arijana Dubovic, successfully graduated in July 2020 at the Faculty of Food Technology and Biotechnology at the University of Zagreb after working with CRISPR design and synthesis in Popovic lab in collaboration with dr. Stuparevic from the Faculty of Food Technology and Biotechnology
July, 2020.
Grant awarded to the PI for 4 years PhD student postion by the Croatian National Science Foundation
December, 2018
5 year project grant awarded to the PI (Croatian National Science Foundation Installation grant UIP-2017-05-5258)
Feb 01, 2018
Farewell to our Erasmus student, Sean Yao Yao Song from University of Ghent in Belgium who joined the group for the 3 months training period on zebrafish husbandry and breeding.
June, 2020