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正常人成纤维细胞中假定的复制起点与核基质的关联

Association of putative origins of replication with the nuclear matrix in normal human fibroblasts.

作者信息

Brylawski B P, Tsongalis G J, Cordeiro-Stone M, May W T, Comeau L D, Kaufman D G

机构信息

Department of Pathology, University of North Carolina, Chapel Hill 27599-7525.

出版信息

Cancer Res. 1993 Sep 1;53(17):3865-8.

PMID:8358710
Abstract

Several metabolic processes, such as DNA organization and replication, transcription, and RNA processing are closely associated with the nuclear matrix. Nuclear matrix attachment regions are nucleotide sequences holding DNA tightly complexed with the nuclear scaffold and are resistant to extractions with detergents and high salt solutions. The role of matrix attachment regions in DNA replication has not been completely clarified, but they have been identified in close association with origins of replication in mammalian cells. We isolated nuclear matrix-associated DNA from normal human fibroblasts synchronized to different phases of the cell cycle and cloned compatible fragments into pUC19. We tested the homology of a fraction of the available clones to DNA replicated at the beginning of the S phase in human fibroblasts. We confirmed that nuclear matrix-associated DNA isolated from cells in G0 and G1 phases of the cell cycle contains sequences that are among the earliest replicated regions in the human genome. This finding supports the hypothesis that matrix attachment regions in human DNA are located in close proximity to origins of DNA replication.

摘要

几种代谢过程,如DNA的组织与复制、转录以及RNA加工,都与核基质密切相关。核基质附着区域是使DNA与核支架紧密结合的核苷酸序列,并且能抵抗去污剂和高盐溶液的抽提。基质附着区域在DNA复制中的作用尚未完全阐明,但已确定它们与哺乳动物细胞中的复制起点密切相关。我们从同步于细胞周期不同阶段的正常人成纤维细胞中分离出与核基质相关的DNA,并将合适的片段克隆到pUC19中。我们测试了一部分可用克隆与人类成纤维细胞S期开始时复制的DNA的同源性。我们证实,从细胞周期G0和G1期细胞中分离出的与核基质相关的DNA包含人类基因组中最早复制区域的序列。这一发现支持了人类DNA中的基质附着区域位于DNA复制起点附近的假说。

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