Mitotic DNA Damage Responses in Drosophila Polyploid Rectal Papillar Cells

Abstract

Mitosis involves the faithful segregation of two identical copies of chromosomes into two daughter cells. This process is highly regulated to maintain genome integrity, as mis-segregation of partial or whole chromosomes can lead to genomic instability. Cells are constantly exposed to both endogenous and exogenous forms of DNA damage, which if left unattended to, can contribute to mitotic errors. Cells therefore possess DNA damage responses (DDRs) which involves enacting cell cycle checkpoints, DNA damage repair, and in cases of extreme damage – cell death or senescence.While several lines of investigation have identified key mechanisms of the DDR during interphase of the cell cycle, there are several key questions that remain with regards to how cells deal with damage that persists into mitosis. Further, there is currently a gap in knowledge on the mechanisms, timing, and conditions in which different aspects of the DDR are active and coordinated. In this dissertation, I will demonstrate how I implemented genetic and imaging tools using our laboratory’s previously established model system, Drosophila rectal papillar cells [hereafter papillar cells]. Using this model, I studied (1) mechanisms of the DDR during mitosis, (2) mechanisms that act in the absence of key DDR components, and (3) novel regulators and protein-protein interactions of the mitotic DDR. This body of work contributes to the growing knowledge of how cells tolerate DNA damage that persists into mitosis.