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ORIGINAL RESEARCH article

Front. Cell Dev. Biol.
Sec. Cell Growth and Division
Volume 12 - 2024 | doi: 10.3389/fcell.2024.1394531
This article is part of the Research Topic DNA Replication Barriers and the Origins of Cancer View all articles

Tyrosyl-DNA phosphodiesterase 2 (Tdp2) repairs DNA-protein crosslinks and protects against double strand breaks in vivo

Provisionally accepted
Ivan Anticevic Ivan Anticevic Cecile Otten Cecile Otten Marta Popovic Marta Popovic *
  • Rudjer Boskovic Institute, Zagreb, Croatia

The final, formatted version of the article will be published soon.

    DNA-protein crosslinks (DPCs) pose a significant challenge to genome stability and cell viability. Efficient repair of DPCs is crucial for preserving genomic integrity and preventing the accumulation of DNA damage. Despite recent advances in our understanding of DPC repair, many aspects of this process, especially at the organismal level, remain elusive. In this study, we used zebrafish as a model organism to investigate the role of TDP2 (tyrosyl-DNA phosphodiesterase 2) in DPC repair. We characterized the two tdp2 orthologs in zebrafish using phylogenetic, syntenic and expression analysis and investigated the phenotypic consequences of tdp2 silencing in zebrafish embryos. We then quantified the effects of tdp2a and tdp2b silencing on cellular DPC levels and DSB accumulation in zebrafish embryos. Our findings revealed that tdp2b is the main ortholog during embryonic development, while both orthologs are ubiquitously present in adult tissues. Notably, the tdp2b ortholog is phylogenetically closer to human TDP2. Silencing of tdp2b, but not tdp2a, resulted in the loss of Tdp2 activity in zebrafish embryos, accompanied by the accumulation of DPCs and DSBs. Our findings contribute to a more comprehensive understanding of DPC repair at the organismal level and underscore the significance of TDP2 in maintaining genome stability.

    Keywords: DNA Repair, DNA-protein crosslinks, Tyrosyl-DNA phosphodiesterase 2 (Tdp2), Zebrafish, Double strand breaks (DSBs)

    Received: 01 Mar 2024; Accepted: 06 Jun 2024.

    Copyright: © 2024 Anticevic, Otten and Popovic. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Marta Popovic, Rudjer Boskovic Institute, Zagreb, 10000, Croatia

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