Structure and Function of a Eukaryotic Centromere

我实验室的长期目标是了解染色体 种族隔离准确的染色体分离对于正常的生长和发育是必不可少的。中的错误 隔离导致唐氏综合症，最常见的遗传性出生缺陷，流产和癌症。 在维持染色体末端（端粒）方面与端粒相关的错误长期以来一直被认为是一种 复制衰老的原因。最近，着丝粒粘连蛋白的丢失和不能结合减数分裂 染色体结合在一起与母亲年龄影响的机制直接相关 其中三体妊娠的概率在40岁时从2%增加到35%。 我们已经鉴定出一种新的结构，它由凝聚素、凝聚素和臂间DNA组成， 包括模式生物S.啤酒。染色质 桶作为一个弹簧在有丝分裂，有助于力平衡机制时，染色体 附着和对齐由纺锤体检查点监控。我们最近发现了一个 着丝粒染色质环产生足以释放的伸展力的机制 靠近纺锤体轴的核小体。这一发现来自于将热力学原理应用于 着丝粒中放射状环的紧密堆积。放射状环被认为是 几乎所有真核生物的染色体组织。环的密度有生物学上的后果 超越了着丝粒。来自紧密堆积环的张力影响DNA结合的亲和力 蛋白质，从而转录控制以及复制的生物化学。我们的目标是扩大我们的 了解DNA环是如何建立的，紧密包装的后果，以及 控制基因组的获取我们使用芽殖酵母结合遗传学，定量 成像、体内生物物理学和计算建模。 相关性（参见说明）; 每一个生物体的基因组都被包装成染色体，这些染色体必须被复制和分离 极其忠诚我们发现了一种由凝聚素和凝聚素组成的新结构， 包围着有丝分裂纺锤体我们的工作将研究臂间染色质在纺锤体中是如何组织的 以及它如何在有丝分裂中发挥作用，有丝分裂是所有真核生物中保守的过程。

The long term goal of my laboratory is to understand the mechanisms responsible for chromosome segregation. Accurate chromosome segregation is essential for normal growth and development. Errors in segregation lead to Down's syndrome, the most frequent inherited birth defect, pregnancy loss, and cancer. Age-related errors in maintaining the ends of chromosomes (telomeres) have been long recognized as a cause of replicative senescence. More recently, loss of centromere cohesin and the inability to bind meiotic chromosomes together has been directly linked to mechanisms responsible for the maternal age affect wherein the probability of a trisomic pregnancy increases from 2% to 35% by the age of 40. We have identified a novel structure composed of cohesin, condensin and pericentric DNA that encompasses the spindle microtubules in metaphase in the model organism, S. cerevisiae. The chromatin barrel acts as a spring in mitosis that contributes to force balance mechanisms when chromosome attachment and alignment are monitored by the spindle checkpoint. We have recently discovered a mechanism in which centromere chromatin loops generate an extensional force sufficient to release nucleosomes proximal to the spindle axis. The discovery comes from applying thermodynamic principles to the close packing of radial loops in the centromere. Radial loops are recognized as the structural basis for the organization of chromosomes in nearly all eukaryotes. The density of loops has biological consequences that transcend the centromere. Tension forces from closely packed loops impact the affinity of DNA binding proteins and thus the biochemistry of transcriptional control as well as replication. Our goal is to extend our understanding of how DNA loops are built, the consequences of close packing, and the implications in regulating access to the genome. We use the budding yeast with a combination of genetics, quantitative imaging, in vivo biophysics and computational modeling. RELEVANCE (See instructions); The genome of every organism is packaged into chromosomes that must be replicated and segregated with exquisite fidelity. We have discovered a new structure composed of cohesin and condensin that surrounds the mitotic spindle. Our work will examine how pericentric chromatin is organized in the spindle and how it functions in mitosis, a conserved process in all eukaryotes.