Open Access Dissertation
Date of Award
Molecular Biology and Genetics
Russell L. Finley, Jr
The Drosophila gene CG14939 encodes a member of a highly conserved family of cyclins, the Y type cyclins, which have not been functionally characterized in any organism. Here I report the generation and phenotypic characterization of a null mutant of CG14939, which we rename Cyclin Y (CycY). I show that the null mutant, CycYE8, is homozygous lethal with most mutant animals arresting during pupal development. The mutant exhibits delayed larval growth and major developmental defects during metamorphosis. Heat shock-induced expression of CycY at different times during development resulted in variable levels of rescue, the timing of which suggests a key function for zygotic CycY during the transition from third instar larvae to prepupae. CycY also plays an essential role during embryogenesis since zygotic null embryos from null mothers fail to hatch into first instar larvae. Furthermore I show that CycY is required for adult viability, especially in males. I provide evidence that the CycY protein (CycY) interacts with Eip63E, a Cyclin-dependent kinase (Cdk) for which no cyclin partner had previously been identified. Like CycY, the Eip63E gene has essential functions during embryogenesis, larval development, and metamorphosis. My data suggest that CycY/Eip63E form a cyclin/Cdk complex that is essential for several developmental processes.
To gain insight into the cellular functions of CycY and to identify signaling pathways to which it belongs, I used RNA interference (RNAi) to knock down CycY expression in specific tissues. I show that CycY is required for wing growth and wing vein development. I also show that CycY genetically interacts with Snr1 and Brm, two components of the Brm ATP-dependent chromatin remodeling complex, and that CycY can physically interact with Snr1. Furthermore, I show that downstream targets of the Brm complex are misregulated in CycY mutants. Taken together, these data suggest that CycY may be involved in gene regulation by modulating Brm complex activity.
Liu, Dongmei, "Determination Of The Essential Functions Of A Conserved Cyclin, Cyclin Y, In Drosophila" (2010). Wayne State University Dissertations. Paper 20.