TIN2, a new regulator of telomere length in human cells

TIN2, a new regulator of telomere length in human cells
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DOI:
10.1038/70508
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发表时间:
1999-12-01
期刊:
影响因子:
30.8
通讯作者:
Campisi, J
Campisi, J
中科院分区:
生物学1区
文献类型:
--
作者:
Kim, SH;Kaminker, P;Campisi, J

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端粒是DNA-蛋白质结构,其覆盖线性染色体并且对于维持基因组稳定性和细胞表型是必需的。利用端粒DNA结合蛋白TRF 1作为诱饵,通过相互作用克隆,我们鉴定了一种新的人类端粒相关蛋白TIN 2。TIN 2在体外和细胞内与TRF 1相互作用,并与TRF 1共定位于细胞核和中期染色体。缺乏氨基末端序列的突变型TIN 2以端粒酶依赖性方式影响延长的人类端粒。我们的研究结果表明,TRF 1是不足以控制人类细胞中的端粒长度,而TIN 2是TRF 1功能的重要介质。
Telomeres are DNA-protein structures that cap linear chromosomes and are essential for maintaining genomic stability and cell phenotype. We identified a novel human telomere-associated protein, TIN2, by interaction cloning using the telomeric DNA-binding-protein TRF1 as a bait. TIN2 interacted with TRF1 in vitro and in cells, and colocalized with TRF1 in nuclei and metaphase chromosomes. A mutant TIN2 that lacks amino-terminal sequences effects elongated human telomeres in a telomerase-dependent manner. Our findings suggest that TRF1 is insufficient for control of telomere length in human cells, and that TIN2 is an essential mediator of TRF1 function.