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Cell. 2013 Oct 10;155(2):345-356. doi: 10.1016/j.cell.2013.09.048.

Super-resolution fluorescence imaging of telomeres reveals TRF2-dependent T-loop formation.

Author information

1
Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, NY 10065, USA.
2
Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA.
3
Department of Chemistry and Chemical Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA.
4
Department of Physics, Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA.
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Contributed equally

Abstract

We have applied a super-resolution fluorescence imaging method, stochastic optical reconstruction microscopy (STORM), to visualize the structure of functional telomeres and telomeres rendered dysfunctional through removal of shelterin proteins. The STORM images showed that functional telomeres frequently exhibit a t-loop configuration. Conditional deletion of individual components of shelterin showed that TRF2 was required for the formation and/or maintenance of t-loops, whereas deletion of TRF1, Rap1, or the POT1 proteins (POT1a and POT1b) had no effect on the frequency of t-loop occurrence. Within the shelterin complex, TRF2 uniquely serves to protect telomeres from two pathways that are initiated on free DNA ends: classical nonhomologous end-joining (NHEJ) and ATM-dependent DNA damage signaling. The TRF2-dependent remodeling of telomeres into t-loop structures, which sequester the ends of chromosomes, can explain why NHEJ and the ATM signaling pathway are repressed when TRF2 is present.

PMID:
24120135
PMCID:
PMC4062873
DOI:
10.1016/j.cell.2013.09.048
[Indexed for MEDLINE]
Free PMC Article
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