Rif2 protects Rap1-depleted telomeres from MRX-mediated degradation in<i>Saccharomyces cerevisiae</i>

Bringas, Fernando R Rosas; Stinus,; Wanders, Lisa; Zoeten, de; Cohn, Marita; Chang, Michael

doi:10.1101/2020.12.30.424824

Cited by 2 publications

(1 citation statement)

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“…Saccharomyces cerevisiae) composed of Mre11, Rad50, and Nbs1 or Xrx2 that initiates the processing of DSBs. It was recently reported that S. cerevisiae MRX can be inhibited by the telomere-associated protein Rif2 [56][57][58]. Rif2p inhibits MRX through an inhibitory motif called MIN, which interacts with the MRX complex through the Rad50 protein [56,57].…”

Section: Of 43mentioning

confidence: 99%

Ccq1 restrains Mre11-mediated degradation of short telomeres

Audry

Runge

2022

Preprint

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Telomeres cap chromosome ends with specialized chromatin composed of DNA repeats bound by a multiprotein complex called shelterin. Fission yeast telomeres can be formed by cleaving a “proto-telomere” bearing 48 bp of telomere repeats to form a new stable chromosomal end that prevents the rapid degradation seen at similar DNA double-strand breaks (DSBs). This end-protection was investigated in viable mutants lacking telomere-associated proteins. Telomerase, the shelterin components Taz1, Rap1, or Poz1 or the telomere-associated protein Rif1 were not required to form a stable chromosome end after cleavage of the proto-telomere. However, cells lacking the fission yeast shelterin component Ccq1 converted the cleaved telomere repeat-capped end to a rapidly degraded DSB. Degradation was greatly reduced by eliminating the nuclease activity of Mre11, a component of the Mre11-Rad50-Nbs1/Xrs2 complex that processes DSBs. These results demonstrate a novel function for Ccq1 to effect end-protection by restraining Mre11-dependent degradation.

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Section: Of 43mentioning

confidence: 99%

Ccq1 restrains Mre11-mediated degradation of short telomeres

Audry

Runge

2022

Preprint

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Mechanism of MRX inhibition by Rif2 at telomeres

et al. 2021

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Specific proteins present at telomeres ensure chromosome end stability, in large part through unknown mechanisms. In this work, we address how the Saccharomyces cerevisiae ORC-related Rif2 protein protects telomere. We show that the small N-terminal Rif2 BAT motif (Blocks Addition of Telomeres) previously known to limit telomere elongation and Tel1 activity is also sufficient to block NHEJ and 5’ end resection. The BAT motif inhibits the ability of the Mre11-Rad50-Xrs2 complex (MRX) to capture DNA ends. It acts through a direct contact with Rad50 ATP-binding Head domains. Through genetic approaches guided by structural predictions, we identify residues at the surface of Rad50 that are essential for the interaction with Rif2 and its inhibition. Finally, a docking model predicts how BAT binding could specifically destabilise the DNA-bound state of the MRX complex. From these results, we propose that when an MRX complex approaches a telomere, the Rif2 BAT motif binds MRX Head in its ATP-bound resting state. This antagonises MRX transition to its DNA-bound state, and favours a rapid return to the ATP-bound state. Unable to stably capture the telomere end, the MRX complex cannot proceed with the subsequent steps of NHEJ, Tel1-activation and 5’ resection.

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Rif2 protects Rap1-depleted telomeres from MRX-mediated degradation inSaccharomyces cerevisiae

Cited by 2 publications

References 109 publications

Ccq1 restrains Mre11-mediated degradation of short telomeres

Ccq1 restrains Mre11-mediated degradation of short telomeres

Mechanism of MRX inhibition by Rif2 at telomeres

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