Mitotic regulators and their effects on Drosophila : chromosome structure during development

Abstract

Variants of the canonical cell cycle are frequently used in nature to accomplish specific developmental goals. In one such variant, the endocycle, synthesis phase alternates with a gap phase without an intervening mitosis, producing cells that have multiple copies of the genome. These cells show diversity in their chromosome structure; at one extreme, the sister chromatids are separate (polyploid) and at the other extreme, the sisters are held together (polytene). The endocycle itself can be modified and these variations are speculated to correlate with the observed differences in chromosome structure. In this thesis, we have analyzed the contribution of mitotic regulators to the endocycle and polytene chromosome structure in Drosophila. We show that morula, a gene required for the transition from polytene to polyploid chromosome structure in Drosophila nurse cells, is a subunit of the anaphase-promoting complex/cyclosome. Increasing levels of cyclin B, a known mitotic target of the APC/C, does not alter the timing of the transition, indicating that CYCLIN B is not the only APC/C target at the polyteny-polyploidy transition. In mitosis, activity of APC/C and POLO lead to the loss of sister-chromatid cohesion and we find that mutants in polo are unable to progress through the polyteny-polyploidy transition. Finally, we find that the cohesin complex, a complex required for the physical attachment of sister chromatids in mitosis, is required for proper polytene chromosome structure in the salivary gland. These results describe a requirement for the cohesin complex in a variant of the cell cycle lacking mitosis and indicate that sister-chromatid cohesion differentiates polytene and polyploid chromosome structures.