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Publication : Resolution of telomere associations by TRF1 cleavage in mouse embryonic stem cells.

First Author  Lisaingo K Year  2014
Journal  Mol Biol Cell Volume  25
Issue  13 Pages  1958-68
PubMed ID  24829382 Mgi Jnum  J:215251
Mgi Id  MGI:5604958 Doi  10.1091/mbc.E13-10-0564
Citation  Lisaingo K, et al. (2014) Resolution of telomere associations by TRF1 cleavage in mouse embryonic stem cells. Mol Biol Cell 25(13):1958-68
abstractText  Telomere associations have been observed during key cellular processes such as mitosis, meiosis, and carcinogenesis and must be resolved before cell division to prevent genome instability. Here we establish that telomeric repeat-binding factor 1 (TRF1), a core component of the telomere protein complex, is a mediator of telomere associations in mammalian cells. Using live-cell imaging, we show that expression of TRF1 or yellow fluorescent protein (YFP)-TRF1 fusion protein above endogenous levels prevents proper telomere resolution during mitosis. TRF1 overexpression results in telomere anaphase bridges and aggregates containing TRF1 protein and telomeric DNA. Site-specific protein cleavage of YFP-TRF1 by tobacco etch virus protease resolves telomere aggregates, indicating that telomere associations are mediated by TRF1. This study provides novel insight into the formation and resolution of telomere associations.
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