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端粒通过染色体特异性而非普遍的复制程序进行复制。

Human telomeres replicate using chromosome-specific, rather than universal, replication programs.

机构信息

Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

出版信息

J Cell Biol. 2012 Apr 16;197(2):253-66. doi: 10.1083/jcb.201112083.

DOI:10.1083/jcb.201112083
PMID:22508510
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3328383/
Abstract

Telomeric and adjacent subtelomeric heterochromatin pose significant challenges to the DNA replication machinery. Little is known about how replication progresses through these regions in human cells. Using single molecule analysis of replicated DNA (SMARD), we delineate the replication programs-i.e., origin distribution, termination site location, and fork rate and direction-of specific telomeres/subtelomeres of individual human chromosomes in two embryonic stem (ES) cell lines and two primary somatic cell types. We observe that replication can initiate within human telomere repeats but was most frequently accomplished by replisomes originating in the subtelomere. No major delay or pausing in fork progression was detected that might lead to telomere/subtelomere fragility. In addition, telomeres from different chromosomes from the same cell type displayed chromosome-specific replication programs rather than a universal program. Importantly, although there was some variation in the replication program of the same telomere in different cell types, the basic features of the program of a specific chromosome end appear to be conserved.

摘要

端粒和相邻的亚端粒异染色质对 DNA 复制机制构成了重大挑战。目前人们对复制过程如何在人类细胞中通过这些区域还知之甚少。使用复制 DNA 的单分子分析 (SMARD)，我们描绘了特定人类染色体端粒/亚端粒的复制程序，即起点分布、终止位点位置以及叉速率和方向，在两个胚胎干细胞 (ES) 细胞系和两种主要的体细胞核型中。我们观察到，复制可以在人类端粒重复序列内启动，但最常通过起源于亚端粒的复制体来完成。没有检测到可能导致端粒/亚端粒脆弱性的叉子进展中的主要延迟或暂停。此外，来自同一细胞类型的不同染色体的端粒显示出染色体特异性的复制程序，而不是通用程序。重要的是，尽管在不同细胞类型中端粒的复制程序存在一些差异，但特定染色体末端的程序的基本特征似乎是保守的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9240/3328383/5d1b2c3571c1/JCB_201112083R_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9240/3328383/cca6de0afbc6/JCB_201112083_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9240/3328383/f9f0e89b626b/JCB_201112083_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9240/3328383/536ac9973530/JCB_201112083_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9240/3328383/3a4d0edf4860/JCB_201112083_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9240/3328383/d40dcd275cc0/JCB_201112083_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9240/3328383/4cd5ece8d1ee/JCB_201112083_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9240/3328383/5d1b2c3571c1/JCB_201112083R_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9240/3328383/cca6de0afbc6/JCB_201112083_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9240/3328383/f9f0e89b626b/JCB_201112083_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9240/3328383/536ac9973530/JCB_201112083_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9240/3328383/3a4d0edf4860/JCB_201112083_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9240/3328383/d40dcd275cc0/JCB_201112083_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9240/3328383/4cd5ece8d1ee/JCB_201112083_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9240/3328383/5d1b2c3571c1/JCB_201112083R_Fig7.jpg

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Genome-wide depletion of replication initiation events in highly transcribed regions.全基因组范围内高度转录区域的复制起始事件耗竭。
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