Structural Reorganization of Nuclear Proteins During Mitosis

Iowa State University, Ames IA

Investigators

Abstract

The long term objective of this study is to determine how nuclear morphology is regulated during the cell cycle and what role nuclear components may play in establishment of the mitotic spindle. Towards this end, the investigators have identified a novel nuclear protein in Drosophila, Skeletor, which reorganizes from chromosomally associated structure at interphase to a spindle-like structure at metaphase. Double and triple labelings of Skeletor, tubulin, and DNA indicate that the Skeletor spindle may precede the establishment of the microtubule spindle. When this structure is perturbed by anti-Skeletor antibody injection, the investigators observe deterioration of nuclear morphology and a significant decrease in nuclear division. Thus, the investigators hypothesize that there exists a nuclear structure that reorganizes during the cell cycle which plays an essential role in mitotic spindle assembly and/or function yet is distinct from the microtubule spindle. This hypothesis is strengthened by the observation that embryonic preparations treated briefly with nocodazole and which are void of microtubules still show an intact albeit somewhat deformed Skeletor spindle. The investigators plan to test this hypothesis by performing a number of experiments designed to answer the following key questions: 1) Do anti-Skeletor antibodies identify a previously undescribed nuclear structure? 2) How does this structure reorganize during the cell cycle and does it provide a guide for establishment of the mitotic spindle? 3) Is Skeletor an integral or associated component of this nuclear structure? 4) Does Skeletor function in signaling or effecting the nuclear reorganization events during the cell cycle? 5) What is the effect of perturbing this structure genetically or by other means? 6) What other components interact with or regulate this structure? The information obtained from these experiments will provide major new insights into nuclear architectural remodeling during the cell cycle and microtubule spindle assembly and function during mitosis.