Conference: Gordon Research Conference in Centromere Biology

着丝粒可能仍然是真核生物基因组中最神秘的区域，尽管它们在真核细胞的每一次分裂中都是染色体分离的关键角色。着丝粒在基因组遗传中的重要性早已被认识到，但它们的性质、组织和变异性一直是个谜。事实上，尽管早在十多年前就对人类基因组进行了“完整测序”，但直到最近才完成了人类着丝粒的第一次组装。这一进展现在使研究人员能够利用这一序列信息来解决着丝粒特性和行为的基本问题。拟议的戈登研究研讨会和会议将激发讨论，以考虑该领域将如何需要以着丝粒DNA序列信息为基础，以了解结构和功能的日益复杂。这次会议将成为着丝粒领域的重要催化剂，以产生一个独特的概念框架来解决这些问题，以及结合基因组、计算和生物信息学方法的工具和技术，以及在分子、细胞和生物水平上的补充功能生物学研究。更广泛的影响包括这项研究的内在价值，因为所有真核细胞在细胞分裂过程中都依赖着丝粒。此外，还将为下一代研究人员提供培训和联网机会。正常的着丝粒功能需要一系列复杂的生化事件来指导染色质和着丝粒的组装，并涉及数百种不同的蛋白质。然而，整合导致功能着丝粒的遗传和生化事件的确切机制在很大程度上仍不清楚。有丝分裂过程中着丝粒的形成依赖于特殊的着丝粒染色质，其中组蛋白H3核小体被含有着丝粒着丝粒蛋白A(CENP-A)的核小体取代。CENP-A未能在每个细胞周期中装载到着丝粒上，最终会导致着丝粒丢失、着丝粒失效、染色体错误分离和细胞死亡。着丝粒功能缺陷和由此导致的染色体分离错误导致染色体非整倍体，这是许多疾病的特征。在过去的十年里，着丝粒研究人员已经确定了一些控制着丝粒蛋白组装和着丝粒染色质表观遗传维持的关键因素。然而，我们对这些因素如何在每个细胞分裂周期的特定位置产生着丝粒缺乏清楚的了解，这次会议和相关研讨会将把研究人员聚集在一起，讨论推进我们对基因组这一重要区域的理解所需的战略方向。这次会议是由分子和细胞生物科学部内的细胞动力学和功能与遗传机制计划共同主办的。这个奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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. 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.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 BiosciencesThis 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.