Telomere dysfunction and cell survival: roles for distinctTIN2-containing complexes Page: 2 of 25
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Telomeres are maintained by three DNA binding proteins, TRF1, TRF2
and POT1, and several associated factors. One factor, TIN2, binds TRF1 and
TRF2 directly and POT1 indirectly. These and two other proteins form a soluble
complex that may be the core telomere-maintenance complex. It is not clear
whether subcomplexes exist or function in vivo. Here, we provide evidence for
two TIN2 subcomplexes with distinct functions in human cells. TIN2 ablation by
RNA interference caused telomere uncapping and p53-independent cell death in
all cells tested. However, we isolated two TIN2 complexes from cell lysates,
each selectively sensitive to a TIN2 mutant (TIN2-13, TIN2-15C). In cells with
wild-type p53 function, TIN2-15C was more potent than TIN2-13 in causing
telomere uncapping and eventual growth arrest. In cells lacking p53 function,
TIN215C more than TIN2-13 caused genomic instability and cell death. Thus,
TIN2 subcomplexes likely have distinct functions in telomere maintenance, and
may provide selective targets for eliminating cells with mutant p53.
Kim et al.
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Kim, Sahn-Ho; Davalos, Albert R.; Heo, Seok-Jin; Rodier, Francis; Beausejour, Christian; Kaminker, Patrick et al. Telomere dysfunction and cell survival: roles for distinctTIN2-containing complexes, article, November 7, 2006; Berkeley, California. (https://digital.library.unt.edu/ark:/67531/metadc897420/m1/2/: accessed April 22, 2019), University of North Texas Libraries, Digital Library, https://digital.library.unt.edu; crediting UNT Libraries Government Documents Department.