The Francis Crick Institute
Genes Dev.-2021-Ruis-1-21 (3).pdf (3.9 MB)

The end protection problem-an unexpected twist in the tail.

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journal contribution
posted on 2021-01-15, 09:43 authored by Phil Ruis, Simon J Boulton
In this perspective, we introduce shelterin and the mechanisms of ATM activation and NHEJ at telomeres, before discussing the following questions: How are t-loops proposed to protect chromosome ends and what is the evidence for this model? Can other models explain how TRF2 mediates end protection? Could t-loops be pathological structures? How is end protection achieved in pluripotent cells? What do the insights into telomere end protection in pluripotent cells mean for the t-loop model of end protection? Why might different cell states have evolved different mechanisms of end protection? Finally, we offer support for an updated t-loop model of end protection, suggesting that the data is supportive of a critical role for t-loops in protecting chromosome ends from NHEJ and ATM activation, but that other mechanisms are involved. Finally, we propose that t-loops are likely dynamic, rather than static, structures.


European Research Council (Grant ID: 742437 - TelMetab, Grant title: ERC 742437 - TelMetab) Crick (Grant ID: 10048, Grant title: Boulton FC001048)