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Rif1 S-acylation mediates DNA double-strand break repair at the inner nuclear membrane

Author

Listed:
  • Gabriele A. Fontana

    (Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66
    ETH Zürich)

  • Daniel Hess

    (Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66)

  • Julia K. Reinert

    (Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66
    University of Basel)

  • Stefano Mattarocci

    (University of Geneva
    Sorbonne Université, CNRS/UPMC, 13 rue Pierre et Marie Curie)

  • Benoît Falquet

    (Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66
    University of Basel)

  • Dominique Klein

    (Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66)

  • David Shore

    (University of Geneva)

  • Nicolas H. Thomä

    (Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66)

  • Ulrich Rass

    (Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66
    University of Sussex, Falmer)

Abstract

Rif1 is involved in telomere homeostasis, DNA replication timing, and DNA double-strand break (DSB) repair pathway choice from yeast to human. The molecular mechanisms that enable Rif1 to fulfill its diverse roles remain to be determined. Here, we demonstrate that Rif1 is S-acylated within its conserved N-terminal domain at cysteine residues C466 and C473 by the DHHC family palmitoyl acyltransferase Pfa4. Rif1 S-acylation facilitates the accumulation of Rif1 at DSBs, the attenuation of DNA end-resection, and DSB repair by non-homologous end-joining (NHEJ). These findings identify S-acylation as a posttranslational modification regulating DNA repair. S-acylated Rif1 mounts a localized DNA-damage response proximal to the inner nuclear membrane, revealing a mechanism of compartmentalized DSB repair pathway choice by sequestration of a fatty acylated repair factor at the inner nuclear membrane.

Suggested Citation

  • Gabriele A. Fontana & Daniel Hess & Julia K. Reinert & Stefano Mattarocci & Benoît Falquet & Dominique Klein & David Shore & Nicolas H. Thomä & Ulrich Rass, 2019. "Rif1 S-acylation mediates DNA double-strand break repair at the inner nuclear membrane," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10349-z
    DOI: 10.1038/s41467-019-10349-z
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    Cited by:

    1. Mischan Vali-Pour & Solip Park & Jose Espinosa-Carrasco & Daniel Ortiz-Martínez & Ben Lehner & Fran Supek, 2022. "The impact of rare germline variants on human somatic mutation processes," Nature Communications, Nature, vol. 13(1), pages 1-21, December.

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