Kim S H, Kaminker P, Campisi J
Department of Cell and Molecular Biology, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
Nat Genet. 1999 Dec;23(4):405-12. doi: 10.1038/70508.
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 co-localized 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.
端粒是一种DNA-蛋白质结构,它覆盖线性染色体,对于维持基因组稳定性和细胞表型至关重要。我们通过以端粒DNA结合蛋白TRF1为诱饵进行相互作用克隆,鉴定出一种新型的人类端粒相关蛋白TIN2。TIN2在体外和细胞内均与TRF1相互作用,并在细胞核和中期染色体中与TRF1共定位。一种缺乏氨基末端序列的突变型TIN2以端粒酶依赖的方式使人类端粒延长。我们的研究结果表明,TRF1不足以控制人类细胞中的端粒长度,并且TIN2是TRF1功能的重要调节因子。