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Rif1 and Rif2 shape telomere function and architecture through multivalent Rap1 interactions

journal contribution
posted on 2023-06-09, 15:11 authored by Tianlai Shi, Richard D Bunker, Stefano Mattarocci, Cyril Ribeyre, Mahamadou Faty, Heinz Gut, Andrea Scrima, Ulrich RassUlrich Rass, Seth M Rubin, David Shore, Nicolas H Thomä
Yeast telomeres comprise irregular TG1?3 DNA repeats bound by the general transcription factor Rap1. Rif1 and Rif2, along with Rap1, form the telosome, a protective cap that inhibits telomerase, counteracts SIR-mediated transcriptional silencing, and prevents inadvertent recognition of telomeres as DNA double-strand breaks. We provide a molecular, biochemical, and functional dissection of the protein backbone at the core of the yeast telosome. The X-ray structures of Rif1 and Rif2 bound to the Rap1 C-terminal domain and that of the Rif1 C terminus are presented. Both Rif1 and Rif2 have separable and independent Rap1-binding epitopes, allowing Rap1 binding over large distances (42-110 Å). We identify tetramerization (Rif1) and polymerization (Rif2) modules that, in conjunction with the long-range binding, give rise to a higher-order architecture that interlinks Rap1 units. This molecular Velcro relies on Rif1 and Rif2 to recruit and stabilize Rap1 on telomeric arrays and is required for telomere homeostasis in vivo.

History

Publication status

  • Published

Journal

Cell

ISSN

0092-8674

Publisher

Elsevier

Issue

6

Volume

153

Page range

1340-1353

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Research groups affiliated with

  • Genome Damage and Stability Centre Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2018-09-24

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