A variable domain of delayed replication in FRAXA fragile X chromosomes: X inactivation-like spread of late replication
A variable domain of delayed replication in FRAXA fragile X chromosomes: X inactivation-like spread of late replication
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DOI：
10.1073/pnas.94.9.4587
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发表时间：
1997-04-29
影响因子：
11.1
通讯作者：
Gartler, SM
中科院分区：
文献类型：
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作者：
Hansen, RS;Canfield, TK;Gartler, SM
在来自正常和脆性X男性的细胞中研究了人X染色体的Xq27部分中DNA复制的时间，以进一步表征脆性X染色体上的复制延迟。通过检查跨越Xq27的几个兆碱基的序列标记位点（STS），我们发现正常活性X染色体的这一部分由两个大区域组成，在成纤维细胞、淋巴细胞和淋巴母细胞样细胞中具有不同的复制时间。着丝粒近端区域在S中复制得非常晚，而远端区域通常复制得稍早并含有FMR 1，我们对脆性X细胞中延迟复制区的分析表明，它延伸了FMR 1的至少400 kb 5'，并且似乎与近端Xq27中非常晚复制的正常区合并，延迟复制的远端边界在不同的脆性X男性中不同，从而确定了在脆性X综合征中可能受影响的三个复制子大小的结构域。延迟复制的最大区域的远端边界位于FMR 1的350和600 kb 3 ′之间。脆性X染色体中晚期复制变异扩散成多个复制子的例子为与位置效应杂色或X染色体失活相关的失活扩散提供了一个模型。
The timing of DNA replication in the Xq27 portion of the human X chromosome was studied in cells derived from normal and fragile X males to further characterize the replication delay on fragile X chromosomes. By examining a number of sequence-tagged sites (STSs) that span several megabases of Xq27, we found this portion of the normal active X chromosome to be composed of two large zones with different replication times in fibroblasts, lymphocytes, and lymphoblastoid cells, The centromere-proximal zone replicates very late in S, whereas the distal zone normally replicates somewhat earlier and contains FMR1, the gene responsible for fragile X syndrome when mutated, Our analysis of the region of delayed replication in fragile X cells indicates that it extends at least 400 kb 5' of FMR1 and appears to merge with the normal zone of very late replication in proximal Xq27, The distal border of delayed replication varies among different fragile X males, thereby defining three replicon-sized domains that can be affected in fragile X syndrome, The distal boundary of the largest region of delayed replication is located between 350 and 600 kb 3' of FMR1. This example of variable spreading of late replication into multiple replicons in fragile X provides a model for the spread of inactivation associated with position-effect variegation or X chromosome inactivation.