(VB and CG are co-first authors)
Germ cells transfer genetic information across generations. Any change in germ line DNA is inherited by succeeding generations. Therefore germ cell DNA must be protected from both internal and external assault. An advantage of sexual reproduction stems from the ability to generate variation by exchange of chromosomal segments during meiosis. During meiosis, hundreds of double-stranded DNA breaks are initiated at once, which if generated in most other cell types would introduce chromosomal aberrations. Germ cells, however, execute the formation of these breaks while preventing their deleterious effects from becoming pervasive throughout the genome. The mechanisms underlying the robustness of germ cells in the face of DNA damage, however, are poorly understood. We have initiated an in vivo CRISPR-Cas9 knockout screen for genes highly enriched in the Drosophila female germ line. Mutants from the screen were assayed for increased gamma-His2Av, a marker for DNA damage. This led to the identification of an uncharacterized but highly conserved protein that contains a Spr-T domain. We have elected to name this gene bedlam, based on its tumorous phenotype. Through experiments in yeast and in cell lines, it has been shown that other members of the Spr-T family are involved in DNA-protein adduct repair. This study aims to characterize a potentially germ line-specific, conserved DNA protein adduct repair pathway, using genetic and molecular biological approaches. Thus, characterizing bedlam function may provide key insights into DNA break repair in multicellular organisms.