A TRF1-controlled common fragile site containing interstitial telomeric sequences.

A TRF1-controlled common fragile site containing interstitial telomeric sequences.
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DOI:
10.1007/s00412-012-0377-6
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发表时间:
2012-10
期刊:
影响因子:
1.6
通讯作者:
de Lange T
de Lange T
中科院分区:
生物学3区
文献类型:
--
作者:
Bosco N;de Lange T

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小鼠端粒已被建议类似于常见的脆性位点(CFS),显示中断TTAGGG荧光原位杂交信号aphidicolin治疗后。这种“脆弱的”端粒表型是由TRF1的缺失诱导的,TRF1是一种结合端粒DNA并促进端粒ds[TTAGGG]n片段有效复制的掩蔽蛋白。在这里,我们表明人类染色体2q14上存在的染色体内部TTAGGG重复序列形成了蚜虫菌素诱导的CFS。TRF1结合并稳定CFS 2q14,但不影响其他CFS,建立2q14作为第一个由序列特异性DNA结合蛋白控制的CFS。这些数据表明,端粒DNA是固有的脆弱,无论其基因组位置,并暗示CFS可以由特定的DNA序列引起。
Mouse telomeres have been suggested to resemble common fragile sites (CFS), showing disrupted TTAGGG fluorescent in situ hybridization signals after aphidicolin treatment. This “fragile” telomere phenotype is induced by deletion of TRF1, a shelterin protein that binds telomeric DNA and promotes efficient replication of the telomeric ds[TTAGGG]n tracts. Here we show that the chromosome-internal TTAGGG repeats present at human chromosome 2q14 form an aphidicolin-induced CFS. TRF1 binds to and stabilizes CFS 2q14 but does not affect other CFS, establishing 2q14 as the first CFS controlled by a sequence-specific DNA binding protein. The data show that telomeric DNA is inherently fragile regardless of its genomic position and imply that CFS can be caused by a specific DNA sequence.
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