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Rif1 maintains telomeres and mediates DNA repair by encasing DNA ends

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posted on 2023-06-09, 15:11 authored by Stefano Mattarocci, Julia K Reinert, Richard D Bunker, Gabriele A Fontana, Tianlai Shi, Dominique Klein, Simone Cavadini, Mahamadou Faty, Maksym Shyian, Lukas Hafner, David Shore, Nicolas H Thomä, Ulrich RassUlrich Rass
In yeast, Rif1 is part of the telosome, where it inhibits telomerase and checkpoint signaling at chromosome ends. In mammalian cells, Rif1 is not telomeric, but it suppresses DNA end resection at chromosomal breaks, promoting repair by nonhomologous end joining (NHEJ). Here, we describe crystal structures for the uncharacterized and conserved ~125-kDa N-terminal domain of Rif1 from Saccharomyces cerevisiae (Rif1-NTD), revealing an a-helical fold shaped like a shepherd's crook. We identify a high-affinity DNA-binding site in the Rif1-NTD that fully encases DNA as a head-to-tail dimer. Engagement of the Rif1-NTD with telomeres proved essential for checkpoint control and telomere length regulation. Unexpectedly, Rif1-NTD also promoted NHEJ at DNA breaks in yeast, revealing a conserved role of Rif1 in DNA repair. We propose that tight associations between the Rif1-NTD and DNA gate access of processing factors to DNA ends, enabling Rif1 to mediate diverse telomere maintenance and DNA repair functions.

History

Publication status

  • Published

File Version

  • Accepted version

Journal

Nature Structural and Molecular Biology

ISSN

1545-9985

Publisher

Nature Research

Issue

7

Volume

24

Page range

588-595

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Research groups affiliated with

  • Genome Damage and Stability Centre Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2018-09-24

First Open Access (FOA) Date

2018-12-07

First Compliant Deposit (FCD) Date

2018-12-07

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