Telomere-associated protein TIN2 is essential for early embryonic development through a telomerase-independent pathway

被引:61
作者
Chiang, YJ
Kim, SH
Tessarollo, L
Campisi, J
Hodes, RJ
机构
[1] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA
[2] NIA, NIH, Bethesda, MD 20892 USA
[3] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA
[4] NCI, Canc Res Ctr, Mouse Canc Genet Program, Frederick, MD 21702 USA
关键词
D O I
10.1128/mcb.24.15.6631-6634.2004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
TIN2 is a negative regulator of telomere elongation that interacts with telomeric DNA repeat binding factor 1 (TRF1) and affects telomere length by a telomerase-dependent mechanism. Here we show that inactivation of the mouse TRF1-interacting protein 2 (TIN2) gene results in early embryonic lethality. We further observed that the embryonic lethality of TIN2 mutant mice was not affected by inactivation of the telomerase reverse transcriptase gene, indicating that embryonic lethality is not the result of telomerase-dependent changes in telomere length or function. Our findings suggest that TIN2 has a role independent of telomere length regulation that is essential for embryonic development and cell viability.
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页码:6631 / 6634
页数:4
相关论文
共 22 条
[1]   Pot1, the putative telomere end-binding protein in fission yeast and humans [J].
Baumann, P ;
Cech, TR .
SCIENCE, 2001, 292 (5519) :1171-1175
[2]   TRF1 is a dimer and bends telomeric DNA [J].
Bianchi, A ;
Smith, S ;
Chong, L ;
Elias, P ;
deLange, T .
EMBO JOURNAL, 1997, 16 (07) :1785-1794
[3]  
Bonin A, 2000, METH MOL B, V158, P121
[4]   Comparison of the human and mouse genes encoding the telomeric protein, TRF1: Chromosomal localization, expression and conserved protein domains [J].
Broccoli, D ;
Chong, L ;
Oelmann, S ;
Fernald, AA ;
Marziliano, N ;
vanSteensel, B ;
Kipling, D ;
LeBeau, MM ;
deLange, T .
HUMAN MOLECULAR GENETICS, 1997, 6 (01) :69-76
[5]   Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2 [J].
Broccoli, D ;
Smogorzewska, A ;
Chong, L ;
deLange, T .
NATURE GENETICS, 1997, 17 (02) :231-235
[6]   Telomerase and the maintenance of chromosome ends [J].
Bryan, TM ;
Cech, TR .
CURRENT OPINION IN CELL BIOLOGY, 1999, 11 (03) :318-324
[7]   Functional interaction between DNA-PKcs and telomerase in telomere length maintenance [J].
Espejel, S ;
Franco, S ;
Sgura, A ;
Gae, D ;
Bailey, SM ;
Taccioli, GE ;
Blasco, MA .
EMBO JOURNAL, 2002, 21 (22) :6275-6287
[8]   Ku acts in a unique way at the mammalian telomere to prevent end joining [J].
Hsu, HL ;
Gilley, D ;
Galande, SA ;
Hande, MP ;
Allen, B ;
Kim, SH ;
Li, GC ;
Campisi, J ;
Kohwi-Shigematsu, T ;
Chen, DJ .
GENES & DEVELOPMENT, 2000, 14 (22) :2807-2812
[9]   TANK2, a new TRF1-associated poly(ADP-ribose) polymerase, causes rapid induction of cell death upon overexpression [J].
Kaminker, PG ;
Kim, SH ;
Taylor, RD ;
Zebarjadian, Y ;
Funk, WD ;
Morin, GB ;
Yaswen, P ;
Campisi, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (38) :35891-35899
[10]   Targeted deletion reveals an essential function for the telomere length regulator Trf1 [J].
Karlseder, J ;
Kachatrian, L ;
Takai, H ;
Mercer, M ;
Hingorani, S ;
Jacks, T ;
de Lange, T .
MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (18) :6533-6541