Binding, Sliding and Function of Cohesin on Sister Chromatids

姐妹染色单体上粘连蛋白的结合、滑动和功能

• 批准号: 10355500
• 负责人: Marc R. Gartenberg
• 金额: $ 38.74万
• 依托单位: RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-12 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10355500
• 关键词: Adopted; Binding; Binding Sites; Biological; Biological Assay; Biological Models; Biology; Caliber; Cancer Etiology; Cells; Centromere; Characteristics; Chromatids; Chromatin; Chromatin Loop; Chromosome Structures; Chromosomes; Complex; DNA; DNA Binding; DNA Repair; DNA-Directed RNA Polymerase; Defect; Destinations; Dimensions; Disease; Distant; Event; Fiber; Gene Expression; Genes; Genetic Transcription; Genome; Genomics; Goals; Health; Human; In Vitro; Individual; Learning; Link; Location; Malignant Neoplasms; Maps; Measurement; Measures; Mediating; Methods; Molecular; Molecular Biology; Motion; Movement; Physiological; Positioning Attribute; Process; Role; Series; Sister Chromatid; Site; Slide; Structure; Walking; Work; Yeasts; arm; base; cohesin; cohesion; developmental disease; experimental study; genome-wide; human disease; novel; promoter; protein complex

PI: Gartenberg, Marc R. PROJECT SUMMARY Cohesin organizes eukaryotic genomes into structures that segregate faithfully between dividing cells. The complex keeps newly replicated sister chromatids together and folds individual chromatids into compact chromosomal structures. Cohesin accomplishes these tasks by holding distant DNA sites in close proximity. Defects in cohesin or cohesin regulators have been linked to cancer and are the cause of developmental diseases known collectively as cohesinopathies. Thus, understanding how cohesin functions will reveal much about chromosome structure as it relates to human health. Cohesin complexes bind numerous chromosomal sites by encircling the DNA of each site in a topological embrace. Many cohesin binding sites lie in and around genes. When the genes are expressed, cohesin must move out of the way of advancing RNA polymerases. How this occurs is not clear. The central goal of this proposal is to understand how cohesin moves on chromosomal arms to adopt positions that achieve structural roles yet permit proper gene expression. The Gartenberg lab recently showed that cohesin translocates on DNA by sliding, and that the complex remains cohesive while in motion. Using yeast as a model system, this proposal aims to determine how the dynamic distribution of cohesin on chromosomal DNA is determined by binding, sliding and function of the complex. Aim 1 uses novel, molecular biology assays to define the dimensions of the DNA channel through cohesin, as well as determine whether the complex embraces one or two chromatids within the same channel. The experiments will determine how the dimensions of the complex limit which obstacles the complex can slide past. Aim 2 uses molecular biology assays to determine how transcription and other ATP-dependent processes regulate cohesin movement, and define the biological consequences when movement is blocked. The experiments will determine the molecular basis and physiological benefit of cohesin accumulating at specific cohesin enrichment sites. Aim 3 uses genome-scale strategies to distinguish between chromosomal sites where cohesin holds sister chromatids together and where it does not. The experiments will yield the first comprehensive maps of cohesin based on the functionality of the complex.

PI：Gartenberg，Marc R. 项目摘要 粘着素将真核基因组组织成忠实分离细胞之间的结构。这 复合物将新复制的姐妹染色质剂组合在一起，并将单个染色单体折叠成紧凑型 染色体结构。粘着蛋白通过将远处的DNA位点靠近接近来完成这些任务。 粘蛋白或粘着蛋白调节剂缺陷已与癌症有关，是发育的原因 统称为粘粘病的疾病。因此，了解粘着蛋白功能将如何揭示大量 关于与人类健康有关的染色体结构。 粘蛋白复合物通过包围拓扑中每个位点的DNA结合了许多染色体位点 拥抱。许多粘蛋白结合位点位于基因和周围。当表达基因时，粘蛋白必须 移出推进RNA聚合酶的方式。这种情况的发生尚不清楚。这个中心目标 建议是了解粘合素如何在染色体臂上移动以采用实现结构的位置 角色却允许适当的基因表达。 Gartenberg实验室最近显示，粘蛋白通过滑动在DNA上易位，并且复合 运动时保持凝聚力。该建议使用酵母作为模型系统，旨在确定 粘蛋白在染色体DNA上的动态分布由结合，滑动和功能确定 复杂的。 AIM 1使用新颖的分子生物学测定法来定义DNA通道的维度 粘蛋白，并确定该复合物是否在同一通道内包含一种或两个染色单体。 实验将确定复杂极限的尺寸如何障碍物可以滑动 过去的。 AIM 2使用分子生物学测定法来确定转录和其他ATP依赖性 过程调节粘蛋白运动，并定义当运动阻塞时的生物学后果。 实验将确定粘着蛋白在 特定的粘着蛋白富集位点。 AIM 3使用基因组规模策略来区分染色体 粘蛋白将姐妹染色单体凝聚在一起而没有的位置。实验将产生第一个 基于复合物的功能，粘蛋白的综合图。

项目成果

Nucleoporin TPR promotes tRNA nuclear export and protein synthesis in lung cancer cells.

• DOI: 10.1371/journal.pgen.1009899
• 发表时间: 2021-11
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Chen M;Long Q;Borrie MS;Sun H;Zhang C;Yang H;Shi D;Gartenberg MR;Deng W
• 通讯作者: Deng W

Swapping the gene-specific and regional silencing specificities of the Hst1 and Sir2 histone deacetylases.

交换 Hst1 和 Sir2 组蛋白脱乙酰酶的基因特异性和区域沉默特异性。

• DOI: 10.1128/mcb.01641-06
• 发表时间: 2007
• 期刊: Molecular and cellular biology
• 影响因子: 5.3
• 作者: Mead,Janet;McCord,Ron;Youngster,Laura;Sharma,Mandakini;Gartenberg,MarcR;Vershon,AndrewK
• 通讯作者: Vershon,AndrewK

Nucleoporin mediated nuclear positioning and silencing of HMR.

核孔蛋白介导的核定位和 HMR 沉默。

• DOI: 10.1371/journal.pone.0021923
• 发表时间: 2011
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Ruben,GiuliaJ;Kirkland,JacobG;MacDonough,Tracy;Chen,Miao;Dubey,RudraN;Gartenberg,MarcR;Kamakaka,RohintonT
• 通讯作者: Kamakaka,RohintonT

Targeted sister chromatid cohesion by Sir2.

• DOI: 10.1371/journal.pgen.1002000
• 发表时间: 2011-02-03
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Wu CS;Chen YF;Gartenberg MR
• 通讯作者: Gartenberg MR

The Protective Role of the Family and Social Support Network in a Sample of HIV-Positive African American Women: Results of a Pilot Study.

家庭和社会支持网络在艾滋病毒呈阳性的非洲裔美国妇女样本中的保护作用：试点研究的结果。

• DOI: 10.1177/0095798402239227
• 发表时间: 2003
• 期刊: The Journal of black psychology
• 作者: Robbins,Michael;Szapocznik,José;Tejeda,Manuel;Samuels,Deanne;Ironson,Gail;Antoni,Michael
• 通讯作者: Antoni,Michael