The GTPase DRG1 controls microtubule dynamics and is involved in chromatin decondensation

Abstract

The mitotic spindle, essential for segregating the sister chromatids into the two evolving daughter cells, is composed of highly dynamic cytoskeletal filaments, the microtubules. The dynamics of microtubules are regulated by numerous microtubule associated proteins. During my PhD project, I identified Developmentally regulated GTP binding protein 1 (DRG1) as a microtubule binding protein with diverse microtubule-associated functions. In vitro, DRG1 can diffuse on microtubules, promotes their polymerization, drives microtubule formation into bundles, and stabilizes microtubules. HeLa cells with reduced DRG1 levels show delayed progression from prophase to anaphase because spindle formation is slowed down. To perform its microtubule-associated functions, DRG1, although being a GTPase, does not require GTP hydrolysis. However, all domains are required as truncated versions show none of the mentioned activities besides microtubule binding. Furthermore, I found that DRG1 is most likely a chromatin decondensation factor. The possible interdependence of mitotic spindle assembly and chromatin decondensation are discussed in this thesis. [untranslated]