NSF Award
2201104
Centromeres remain perhaps the most enigmatic regions of the eukaryotic genome, despite their critical role as the foundation for chromosome segregation during every eukaryotic cell division. The importance of centromeres in genome inheritance has long been recognized, but their properties, organization, and variability have remained mysterious. Indeed, despite the “complete sequencing” of the human genome more than a decade ago, it was only recently that the first assembly of a human centromere was completed. This advance is now allowing researchers to harness this sequence information to tackle fundamental questions on centromere properties and behavior. The proposed Gordon Research Seminar and Conference will stimulate discussions to consider how the field will need to build upon centromere DNA sequence information towards understanding the increasing complexity in structure and function. This conference will act as an important catalyst for the centromere field to generate a unique conceptual framework to address these questions, together with tools and technologies that combine genome, computational and bioinformatics approaches, and complementary functional biological studies at the molecular, cellular, and organismal levels. The Broader Impacts of effort include the intrinsic merit of the research as all eukaryotic cells rely on centromeres during cell division. In addition, training and networking opportunities will be provided for the next generation of researchers. <br/><br/>Proper centromere function requires a complex cascade of biochemical events to direct chromatin and kinetochore assembly and involves hundreds of different proteins. However, the precise mechanisms that integrate the genetic and biochemical events leading to functional centromeres are still largely unknown. Kinetochore formation during mitosis depends upon the specialized centromeric chromatin in which histone H3 nucleosomes are replaced with nucleosomes containing the centromeric histone Centromere Protein A (CENP-A). Failure to load CENP-A into centromeres each cell cycle ultimately leads to centromere loss, kinetochore failure, chromosome mis-segregation and cell death. Defects in centromere function and the resulting chromosome segregation errors lead to chromosome aneuploidy, a hallmark of many afflictions. Over the past decade, centromere researchers have identified some of the key factors that control centromere protein assembly and the epigenetic maintenance of centromeric chromatin. However, we lack a clear understanding of how these factors come together to generate centromeres at a specific locus through each cell division cycle and this conference and associated seminar will bring together researchers to discuss strategic directions that are needed to advance our understanding of this important region of the genome.<br/>This conference is co-sponsored by the Cellular Dynamics and Function together with the Genetic Mechanisms program, both within the Division of Molecular and Cellular Biosciences<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
