Loss of the homologous recombination gene <i>rad51</i> leads to Fanconi anemia-like symptoms in zebrafish

Abstract

Significance The homologous recombination protein RAD51 has been extensively studied in prokaryotes and lower eukaryotes. However, there is a significant lack of knowledge of the role of this protein and its regulation in an in vivo context in vertebrates. Here we report the first viable vertebrate mutant model of rad51 in zebrafish. These mutant fish enabled us to confirm the recently discovered role of RAD51 in Fanconi anemia pathogenesis. We report that p53-linked embryonic stem cell defects directly lead to hematological impairments later in life. Comutation of rad51 with p53 rescues the observed hematological defects, but predisposes the fish to early tumor development. The application of this model opens new possibilities to advance Fanconi anemia drug discovery. </jats:p