View Program - 63rd Annual Drosophila Research Conference

Successful transmission of genetic information from one generation to the next requires germline stem cells to maintain their genomic integrity. Germ cells with DNA damage, such as double strand breaks (DSBs), are largely eliminated. The pathway that works to eliminate cells containing DNA damage has been well studied in the soma. The upstream protein kinase Chk2 phosphorylates P53 which leads to apoptosis. However, in the germline, Chk2 is necessary for elimination of germline cells while P53 is not. This leads to the question: what is downstream of Chk2 in the germline? We used FLP/FRT to efficiently induce DSBs in the male germline. We find that mutation of any of Chk2’s domains, including its kinase function, eliminate its DSB checkpoint function in the germline. String (stg), a positive regulator of cell cycle progression, is a known target of Chk2 in some systems. If Chk2 negatively regulated Stg in response to a DSB, we reasoned that overexpression of stg⁺ might bypass the Chk2 effect and mimic the effect of chk2 mutants. We found this to be true, strongly suggesting that Chk2 acts through Stg in the germline to block cell cycle progression, ultimately leading to the elimination of cells with damaged DNA.

Maintenance of genomic integrity in the male germline of Drosophila melanogaster