Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing 401122, China; Department of Biology, Northeastern University, Boston, MA 02115, USA.
Department of Biology, Northeastern University, Boston, MA 02115, USA.
Mutat Res. 2013 Mar-Apr;743-744:151-159. doi: 10.1016/j.mrfmmm.2012.10.003. Epub 2012 Dec 1.
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.
斑马鱼（Danio rerio）已成为研究胚胎发育的一种流行的脊椎动物模型，因为它具有其他模型系统所没有的独特优势。斑马鱼与包括人类在内的其他脊椎动物共享许多基因功能，这使得斑马鱼成为研究癌症病因的有用系统。然而，使用成年或胚胎斑马鱼对 DNA 损伤和修复途径进行系统研究尚未得到广泛报道。斑马鱼基因组包含真核生物中几乎所有参与不同 DNA 修复途径的基因，包括直接逆转（DR）、错配修复（MMR）、核苷酸切除修复（NER）、碱基切除修复（BER）、同源重组（HR）、非同源末端连接（NHEJ）和跨损伤合成（TLS）。它还包括 p53 介导的损伤识别途径的基因。因此，斑马鱼为深入了解 DNA 损伤和修复机制提供了理想的模型，特别是在胚胎发育过程中。本文综述了斑马鱼中不同 DNA 损伤和修复研究的最新工作，特别强调了 BER 在斑马鱼早期胚胎发育中的作用。AP 内切酶 1（Apex1）是 BER 途径中的关键蛋白，不仅调节 BER，还调节环腺苷酸反应结合蛋白（Creb1），后者本身调节约 25%的真核生物编码序列。此外，Apex1 还间接调节 p53 的水平。由于这些发现也发生在鼠 B 细胞中，它们说明了斑马鱼系统在阐明基本机制方面的有用性。
