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Profiling DNA Replication Timing Using Zebrafish as an In Vivo Model System
Published on: April 30, 2018
Zebrafish as a model system to study DNA damage and repair
De-Sheng Pei1, Phyllis R Strauss2
1Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing 401122, China; Department of Biology, Northeastern University, Boston, MA 02115, USA.
Abstract:
Zebrafish (Danio rerio) have become a popular vertebrate model to study embryological development, because of unique advantages not found in other model systems. Zebrafish share many gene functions with other vertebrates including humans, making zebrafish a useful system for studying cancer etiology. However, systematic studies of DNA damage and repair pathways using adult or embryonic zebrafish have not been extensively reported. The zebrafish genome contains nearly all the genes involved in different DNA repair pathways in eukaryotes, including direct reversal (DR), mismatch repair (MMR) nucleotide excision repair (NER), base excision repair (BER), homologous recombination (HR), non-homologous end joining (NHEJ) and translesion synthesis (TLS). It also includes the genes of the p53-mediated damage recognition pathway. Therefore, zebrafish provide an ideal model for gaining fundamental insights into mechanisms of DNA damage and repair, especially during embryological development. This review introduces recent work on different DNA damage and repair studies in zebrafish, with special emphasis on the role of BER in zebrafish early embryological development. AP endonuclease 1 (Apex1), a critical protein in the BER pathway, not only regulates BER but also controls cyclic AMP response binding protein (Creb1), which itself regulates ∼25% of eukaryotic coding sequences. In addition, Apex1 indirectly regulates levels of p53. As these findings also occur in murine B cells, they illustrate the usefulness of the zebrafish system in elucidating fundamental mechanisms.
Insights
Zebrafish are ideal models for studying DNA damage and repair, particularly base excision repair (BER) during development. Research highlights AP endonuclease 1
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- Zebrafish (Danio rerio) are valuable vertebrate models for embryological development and human disease studies, including cancer etiology.
- Despite sharing gene functions with humans, systematic studies on DNA damage and repair pathways in zebrafish are limited.
- The zebrafish genome encompasses most eukaryotic DNA repair pathways (e.g., BER, NER, HR) and the p53 pathway.
Purpose of the Study:
- To review recent DNA damage and repair studies in zebrafish.
- To emphasize the role of Base Excision Repair (BER) in early zebrafish embryological development.
- To explore the function of AP endonuclease 1 (Apex1) in DNA repair and its regulatory roles.
Main Methods:
- Literature review of DNA damage and repair studies in zebrafish.
- Focus on the Base Excision Repair (BER) pathway and its components.
- Analysis of the regulatory functions of AP endonuclease 1 (Apex1).
Main Results:
- Zebrafish possess comprehensive DNA repair machinery, making them suitable for studying these pathways.
- Base Excision Repair (BER) plays a significant role in zebrafish early embryological development.
- AP endonuclease 1 (Apex1) is crucial for BER and regulates Creb1 and p53 levels, similar to findings in murine B cells.
Conclusions:
- Zebrafish offer a powerful model for fundamental insights into DNA damage and repair mechanisms.
- The study underscores the importance of BER and Apex1 in zebrafish development.
- Findings in zebrafish have implications for understanding DNA repair in other vertebrates, including humans.

