Telomere dysfunction and cell survival [electronic resource] : roles for distinctTIN2-containing complexes
- Washington, D.C. : United States. Dept. of Energy, 2006.
Oak Ridge, Tenn. : Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy.
- Additional Creators:
- United States. Department of Energy
National Institutes of Health (U.S.)
United States. Department of Energy. Office of Scientific and Technical Information
- 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.
- Published through SciTech Connect.
Journal of Cell Biology 181 3 ISSN 0021-9525; JCLBA3 FT
Campisi, Judith; Kim, Sahn-Ho; Kaminker, Patrick; Beausejour, Christian; Davalos, Albert R.; Heo, Seok-Jin; Rodier, Francis.
Ernest Orlando Lawrence Berkeley NationalLaboratory, Berkeley, CA (US)
- Funding Information:
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