Anticheckpoint pathways at telomeres in yeast.

Nature Structural & Molecular Biology
Cyril Ribeyre, D Shore

Abstract

Telomeres hide (or 'cap') chromosome ends from DNA-damage surveillance mechanisms that arrest the cell cycle and promote repair, but the checkpoint status of telomeres is not well understood. Here we characterize the response in Saccharomyces cerevisiae to DNA double-strand breaks (DSBs) flanked by varying amounts of telomeric repeat sequences (TG(1-3)). We show that even short arrays of TG(1-3) repeats do not induce G2/M arrest. Both Rif1 and Rif2 are required for capping at short, rapidly elongating ends, yet are largely dispensable for protection of longer telomeric arrays. Rif1 and Rif2 act through parallel pathways to block accumulation of both RPA and Rad24, activators of checkpoint kinase Mec1 (ATR). Finally, we show that Rif function is correlated with an 'anticheckpoint' effect, in which checkpoint recovery at an adjacent unprotected end is stimulated, and we provide insight into the molecular mechanism of this phenomenon.

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Citations

Mar 19, 2013·Chromosoma·Cyril Ribeyre, David Shore
Jun 5, 2013·Cold Spring Harbor Perspectives in Biology·Christopher J WebbVirginia A Zakian
Sep 17, 2013·PLoS Genetics·Gal Hagit RomanoMartin Kupiec
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Mar 15, 2013·The Journal of Biological Chemistry·Lin FengJunjie Chen
Apr 12, 2016·Frontiers in Genetics·Stefano MattarocciDavid Shore
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Feb 28, 2021·Molecular Cell·Zachary W KocklerAnna Malkova

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