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BRCA1\/BRCA2-containing complex subunit 3 (BRCC3), also known as BRCC36, functions within various multiprotein complexes to mediate diverse biological processes. However, the physiological role of BRCC3 in vertebrates, as well as the underlying mechanisms that govern its activity, are not well understood. To explore these questions, we generated brcc3-knockout zebrafish using CRISPR\/Cas9 gene-editing technology. While brcc3 mutant zebrafish appear phenotypically normal and remain fertile, they exhibit significantly increased rates of mortality and deformity following exposure to DNA damage. Furthermore, embryos lacking Brcc3 display heightened p53 signaling, elevated \u03b3-H2AX levels, and increased apoptosis in response to DNA-damaging agents such as ultraviolet (UV) light and Etoposide (ETO). Notably, genetic inactivation of p53 or pharmacological inhibition of Ataxia-telangiectasia mutated (ATM) activity rescues the hypersensitivity to UV and ETO observed in Brcc3-deficient embryos. These findings suggest that Brcc3 plays a critical role in DNA damage response (DDR), promoting cell survival during embryogenesis. Additionally, brcc3-null mutant zebrafish offer a promising vertebrate model for real-time monitoring of DSBs.<\/jats:p>","DOI":"10.3390\/ijms252212108","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T08:01:27Z","timestamp":1731312087000},"page":"12108","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Loss of Brcc3 in Zebrafish Embryos Increases Their Susceptibility to DNA Damage Stress"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2074-9472","authenticated-orcid":false,"given":"Zhengyang","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Marine Drugs (Ocean University of China), Chinese Ministry of Education, and School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6051-7525","authenticated-orcid":false,"given":"Caixia","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs (Ocean University of China), Chinese Ministry of Education, and School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanpeng","family":"Zhai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs (Ocean University of China), Chinese Ministry of Education, and School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4982-7549","authenticated-orcid":false,"given":"Yan","family":"Bai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs (Ocean University of China), Chinese Ministry of Education, and School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongying","family":"Wang","sequence":"additional","affiliation":[{"name":"Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, Key Laboratory of State Ethnic Affairs Commission for Biological Technology, College of Life Sciences, South-Central Minzu University, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8252-6289","authenticated-orcid":false,"given":"Xiaozhi","family":"Rong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs (Ocean University of China), Chinese Ministry of Education, and School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1080\/15384047.2015.1046022","article-title":"The interplay between DNA repair and autophagy in cancer therapy","volume":"16","author":"Zhang","year":"2015","journal-title":"Cancer Biol. 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