A systematic knowledge of the roles of DNA repair genes at the level of the organism has been limited due to the lack of appropriate experimental approaches using animal model systems. Zebrafish has become a powerful vertebrate genetic model system with availability due to the ease of genome editing and large-scale phenotype screening. Here, we generated zebrafish mutants for 32 DNA repair and replication genes through multiplexed CRISPR/Cas9-mediated mutagenesis. Large-scale phenotypic characterization of our mutant collection revealed that three genes (atad5a, ddb1, pcna) are essential for proper embryonic development and hematopoiesis; seven genes (apex1, atrip, ino80, mre11a, shfm1, telo2, wrn) are required for growth and development during juvenile stage and six genes (blm, brca2, fanci, rad51, rad54l, rtel1) play critical roles in sex development. Furthermore, mutation in six genes (atad5a, brca2, polk, rad51, shfm1, xrcc1) displayed hypersensitivity to DNA damage agents. Our zebrafish mutant collection provides a unique resource for understanding of the roles of DNA repair genes at the organismal level.Copyright © 2021. Published by Elsevier B.V.
About The Expert
Unbeom Shin
Khriezhanuo Nakhro
Chang-Kyu Oh
Blake Carrington
HeaIn Song
Gaurav K Varshney
Yeongjae Kim
Hyemin Song
Sangeun Jeon
Gabrielle Robbins
Sangin Kim
Suhyeon Yoon
Yong Jun Choi
Yoo Jung Kim
Shawn Burgess
Sukhyun Kang
Raman Sood
Yoonsung Lee
Kyungjae Myung
References
PubMed