Berezney R, Mortillaro M J, Ma H, Wei X, Samarabandu J
Department of Biological Sciences, State University of New York at Buffalo 14260, USA.
Int Rev Cytol. 1995;162A:1-65. doi: 10.1016/s0074-7696(08)61228-0.
While significant progress has been made in elucidating molecular properties of specific genes and their regulation, our understanding of how the whole genome is coordinated has lagged behind. To understand how the genome functions as a coordinated whole, we must understand how the nucleus is put together and functions as a whole. An important step in that direction occurred with the isolation and characterization of the nuclear matrix. Aside from the plethora of functional properties associated with these isolated nuclear structures, they have enabled the first direct examination and molecular cloning of specific nuclear matrix proteins. The isolated nuclear matrix can be used for providing an in vitro model for understanding nuclear matrix organization in whole cells. Recent development of high-resolution and three-dimensional approaches for visualizing domains of genomic organization and function in situ has provided corroborative evidence for the nuclear matrix as the site of organization for replication, transcription, and post-transcriptional processing. As more is learned about these in situ functional sites, appropriate experiments could be designed to test molecular mechanisms with the in vitro nuclear matrix systems. This is illustrated in this chapter by the studies of nuclear matrix-associated DNA replication which have evolved from biochemical studies of in vitro nuclear matrix systems toward three-dimensional computer image analysis of replication sites for individual genes.
尽管在阐明特定基因的分子特性及其调控方面已取得重大进展，但我们对整个基因组如何协调的理解仍滞后。为了理解基因组如何作为一个协调的整体发挥功能，我们必须了解细胞核是如何组装以及作为一个整体发挥功能的。朝着这个方向迈出的重要一步是核基质的分离和表征。除了与这些分离的核结构相关的大量功能特性外，它们还使得首次能够直接检测和分子克隆特定的核基质蛋白。分离的核基质可用于提供一个体外模型，以了解全细胞中的核基质组织。用于原位可视化基因组组织和功能域的高分辨率和三维方法的最新进展，为核基质作为复制、转录和转录后加工的组织位点提供了确凿证据。随着对这些原位功能位点的了解越来越多，可以设计适当的实验，利用体外核基质系统来测试分子机制。本章通过对核基质相关DNA复制的研究来说明这一点，这些研究已从体外核基质系统的生化研究发展到对单个基因复制位点的三维计算机图像分析。
