The role of corp in apoptosis following DNA damage. Riddhita Chakraborty, Simon W. Titen, Kent G. Golic. Department of Biology, University of Utah, Salt Lake City, UT.

   In most cells, an unrepaired DNA double-strand break leads to apoptosis, which serves to restrict the propagation of genetic aberrations caused by replication and rearrangement of damaged DNA. However, some cells manage to escape apoptosis and continue to divide. We are interested in understanding the genetic mechanisms that regulate a cell's life or death decision in response to unrepairable DNA damage. Through a misexpression/overexpression screen (EP) in the developing eye, we identified a gene, companion of reaper (corp) whose overexpression strongly enhanced the survival of cells in the eye that carry irreparable DNA damage in the form of a single telomere loss. We show, by TUNEL staining, that corp overexpression blocks apoptosis following DNA damage. Knockdown or mutation of corp produced the opposite effect, giving complete ablation of the eye due to massive cell death following telomere loss. Next, we studied the effect of corp overexpression on transmission of healed chromosomes through the germline. Following telomere loss in the male germline, a chromosome can be healed by addition of a new telomere, and recovered in offsprings at a measurable frequency. We observed that corp overexpression blocks the recovery of broken-and-healed chromosomes from the male germline. Thus, corp seems to produce opposite effects on cells that have experienced telomere loss in the soma versus the germline. This finding is, however, quite similar to the effects of p53 mutants, which increase somatic survival of cells that have lost a telomere, but prevent transmission of broken-and-healed chromosomes in the germline. Thus, we propose that Corp is a negative regulator of p53. In support, we found that in a corp p53 double mutant, p53 is epistatic to corp. Interestingly, previous works demonstrate that the corp gene is a transcriptional target of p53, and that many of the proteins that physically interact with Corp are members of the proteasome complex. We propose that Corp promotes degradation of p53, perhaps playing a role in flies that is similar to the role of Mdm2 in mammals.