NUCLEAR MATRIX STRUCTURE AND DNA REPLICATION

细胞核是所有生物遗传信息的储存库 包括人类在内的真核细胞。尽管有相当大的进展， 在定义主要基因组功能的基本分子特性方面， DNA复制，转录，RNA剪接和加工， 了解这些过程是如何组织和管理的 细胞核的范围非常有限。 同样，虽然 DNA背后的遗传密码（核苷酸序列）早已被 我们对DNA组成染色质的理解 细胞核中的高级结构仍处于起步阶段。 然而，在几个领域取得的进展让我们有理由感到乐观 关于未来的成功。 制定适当的方法， 核结构的三维基础， 灵敏的功能检测系统，如原位荧光 DNA杂交（FISH）和荧光显微镜检测 复制站点是未来的希望之一。 本实验室 一直在研究核基质及其在DNA复制中的作用， 15年 现在，基本的基础暗示核矩阵， 一个DNA复制组织的地点已经确定，我们现在 把我们的注意力集中在细胞内复制的三维组织上， 原子核 通过将这些3D方法与强大的技术相结合， 多维计算机图像分析和FISH，我们正在 3-D DNA复制位点定位的进展。 使用 染色体11组DNA探针将进一步使我们能够确定 11号染色体DNA序列的三维组织及序列定位 存在于各个复制站点。 主要方向是 （1）研究了三维空间组织结构， 细胞核中的DNA复制位点;（2）蛋白质的定位 在复制位点的3-D;（3）在基因序列的3-D映射， 人类11号染色体的细胞核;（4）绘制基因复制图 人类11号染色体的三维图像

The cell nucleus is the repository for the genetic information of all eucaryotic cells including that of man. Despite considerable progress in defining basic molecular properties of the primary genomic functions of DNA replication, transcription, and RNA splicing and processing, our knowledge of how these processes are organized and regulated within the confines of the cell nucleus is extremely limited. Similarly, although the genetic code behind the DNA (the nucleotide sequence) has long been broken, our understanding of the organization of this DNA into chromatin and higher order structures in the cell nucleus is still in its infancy. Progress in several areas, however, gives one reason to be optimistic about future success. Development of appropriate methods to examine the three dimensional basis of nuclear architecture coupled with new and sensitive detection systems for function, such as fluorescence in situ hybridization (FISH) and fluorescence microscopic detection of DNA replication sites are among the hopes of the future. Our laboratory has been studying the nuclear matrix and its role in DNA replication for over 15 years. Now that basic groundwork implicating the nuclear matrix as a site for the organization of DNA replication has been set, we are now focusing our attention on the 3-D organization of replication in the cell nucleus. By combining these 3-D approaches with the powerful techniques of multi-dimensional computer image analysis and FISH, we are making progress in mapping the DNA replication sites in 3-D. Use of a chromosome 11 set of DNA probes will further enable us to determine the DNA sequence organization of chromosome 11 in 3-D and map the sequences present at individual replication sites. The major directions to be pursued in this project include : (1) Study of the 3-D organization of DNA replication sites in the cell nucleus; (2) Localization of proteins at replication sites in 3-D; (3) 3-D mapping of gene sequences in the cell nucleus for human chromosome 11; (4) Map the replication of genes for human chromosome 11 in 3-D.