Wang, Lin-Ing. Regulation of sister centromere fusion and meiotic spindle assembly in Drosophila oocytes. Retrieved from https://doi.org/doi:10.7282/t3-8p8g-4g68
DescriptionAccurate meiotic chromosome segregation prevents aneuploidy that can cause developmental problems and lead to infertility. The majority of errors causing aneuploidy in gametes are maternal in origin due to several innate differences in female meiosis. In contrast to mitosis and male meiosis, bi-polar spindles in female meiosis are assembled in the absence of centrosomes. Instead, the chromosomes direct bi-polar spindle assembly. Abnormalities in spindle formation or structure can cause non-disjunction of the chromosomes. To understand the mechanisms of proper chromosome segregation in female meiosis, I focused on sister centromere cohesion and spindle assembly in Drosophila oocytes. One important mechanism for proper chromosome segregation in meiosis is that the sister chromatids co-orient via sister centromere fusion, resulting in microtubule attachment to a shared spindle pole. This phenomenon is unique to meiosis I, and is well-studied in budding and fission yeast, it remains unclear how it is regulated in other organisms.
Previously our lab has identified two proteins that are required for sister centromere fusion. I characterized these two genes and surprisingly found they regulate sister centromere fusion by two different mechanisms. SPC105R, a kinetochore protein, regulates centromere fusion by recruiting proteins that protect cohesins. Protein phosphatase 1 (PP1), on the other hand, regulates this phenomenon through antagonizing proteins that stabilize microtubule attachment. The latter result suggests that stable microtubule attachment in metaphase I is the prerequisite to release sister centromere fusion without cohesin removal before metaphase II.
The chromosomal passenger complex (CPC) has four subunits (INCENP, Aurora B, Borealin and Survivin/Deterin) and it is essential for spindle assembly in Drosophila oocytes. I made several separation-of-function mutations within the Incenp subunit of the CPC and found that interactions with Heterochromatin Protein 1 (HP1) are key to direct CPC-dependent spindle assembly in oocytes. HP1 firstly recruits the CPC to chromosomes through interacting with Borealin, and this interaction is also required for building the central spindle, the central overlap region of the microtubules. Additionally, I found evidence that HP1 interacts directly with INCENP within the central spindle in oocytes to promote homologous chromosome bi-orientation. These results give rise to a model where HP1 could be a novel CPC targeting subunit and reveals a mechanism for how the CPC mediates chromosome-mediated spindle assembly.