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Pot1 and cell cycle progression cooperate in telomere length regulation

Nature Structural & Molecular Biology volume 15, pages 79–84 (2008)Cite this article

Abstract

Removal of the vertebrate telomere protein Pot1 results in a DNA damage response and cell cycle arrest. Here we show that loss of chicken Pot1 causes Chk1 activation, and inhibition of Chk1 signaling prevents the cell cycle arrest. However, arrest still occurs after disruption of ATM, which encodes another DNA damage response protein. These results indicate that Pot1 is required to prevent a telomere checkpoint mediated by another such protein, ATR, that is most likely triggered by the G-overhang. We also show that removal of Pot1 causes exceptionally rapid telomere growth upon arrest in late S/G2 of the cell cycle. However, release of the arrest slows both telomere growth and G-overhang elongation. Thus, Pot1 seems to regulate telomere length and G-overhang processing both through direct interaction with the telomere and by preventing a late S/G2 delay in the cell cycle. Our results reveal that cell cycle progression is an important component of telomere length regulation.

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Figure 1: Activation of Chk1 signaling after Pot1 removal.
Figure 2: ATM is dispensable for checkpoint activation in response to Pot1 loss.
Figure 3: Increase in telomere length and G-overhang signal in Er-Pot1 cells.
Figure 4: Inhibition of the late S/G2 checkpoint reduces the rate of telomere and G-overhang elongation.

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Acknowledgements

We thank C. Morrison (National University of Ireland) for helpful comments and for providing the ATM gene targeting constructs, D. Gillespie (Beatson Institute for Cancer Research) for the chicken Chk2 antibody and Y. Sanchez (Dartmouth Medical School) for helpful discussions. This work was supported by US National Institutes of Health grant GM041803 to C.M.P.

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Authors and Affiliations

  1. Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, PO Box 0524, Cincinnati, 45267-0524, Ohio, USA

    Dmitri Churikov & Carolyn M Price

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  1. Dmitri Churikov
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D.C. and C.M.P. designed the research; D.C. performed the experiments; C.M.P. wrote the article.

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Correspondence to Carolyn M Price.

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Churikov, D., Price, C. Pot1 and cell cycle progression cooperate in telomere length regulation. Nat Struct Mol Biol 15, 79–84 (2008). https://doi.org/10.1038/nsmb1331

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