TIN2, a new regulator of telomere length in human cells

被引:417
作者
Kim, SH [1 ]
Kaminker, P [1 ]
Campisi, J [1 ]
机构
[1] Lawrence Berkeley Natl Lab, Dept Cell & Mol Biol, Berkeley, CA 94720 USA
关键词
D O I
10.1038/70508
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页码:405 / 412
页数:8
相关论文
共 47 条
  • [21] Stn1, a new Saccharomyces cerevisiae protein, is implicated in telomere size regulation in association with Cdc13
    Grandin, N
    Reed, SI
    Charbonneau, M
    [J]. GENES & DEVELOPMENT, 1997, 11 (04) : 512 - 527
  • [22] Telomere length regulation
    Greider, CW
    [J]. ANNUAL REVIEW OF BIOCHEMISTRY, 1996, 65 : 337 - 365
  • [23] TRF1 promotes parallel pairing of telomeric tracts in vitro
    Griffith, J
    Bianchi, A
    de Lange, T
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1998, 278 (01) : 79 - 88
  • [24] Mammalian telomeres end in a large duplex loop
    Griffith, JD
    Comeau, L
    Rosenfield, S
    Stansel, RM
    Bianchi, A
    Moss, H
    de Lange, T
    [J]. CELL, 1999, 97 (04) : 503 - 514
  • [25] TELOMERES SHORTEN DURING AGING OF HUMAN FIBROBLASTS
    HARLEY, CB
    FUTCHER, AB
    GREIDER, CW
    [J]. NATURE, 1990, 345 (6274) : 458 - 460
  • [26] James P, 1996, GENETICS, V144, P1425
  • [27] SPECIFIC ASSOCIATION OF HUMAN TELOMERASE ACTIVITY WITH IMMORTAL CELLS AND CANCER
    KIM, NW
    PIATYSZEK, MA
    PROWSE, KR
    HARLEY, CB
    WEST, MD
    HO, PLC
    COVIELLO, GM
    WRIGHT, WE
    WEINRICH, SL
    SHAY, JW
    [J]. SCIENCE, 1994, 266 (5193) : 2011 - 2015
  • [28] Both Rb/p16INK4a inactivation and telomerase activity are required to immortalize human epithelial cells
    Kiyono, T
    Foster, SA
    Koop, JI
    McDougall, JK
    Galloway, DA
    Klingelhutz, AJ
    [J]. NATURE, 1998, 396 (6706) : 84 - 88
  • [29] C-TERMINAL TRUNCATION OF RAP1 RESULTS IN THE DEREGULATION OF TELOMERE SIZE, STABILITY, AND FUNCTION IN SACCHAROMYCES-CEREVISIAE
    KYRION, G
    BOAKYE, KA
    LUSTIG, AJ
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1992, 12 (11) : 5159 - 5173
  • [30] Telomerase and chromosome end maintenance
    Lingner, J
    Cech, TR
    [J]. CURRENT OPINION IN GENETICS & DEVELOPMENT, 1998, 8 (02) : 226 - 232