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

Fontana, Gabriele A, Hess, Daniel, Reinert, Julia K, Mattarocci, Stefano, Falquet, Benoît, Klein, Dominique, Shore, David, Thomä, Nicolas H and Rass, Ulrich (2019) Rif1 S-acylation mediates DNA double-strand break repair at the inner nuclear membrane. Nature Communications, 10 (2535). pp. 1-14. ISSN 2041-1723

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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.

Item Type: Article
Keywords: DNA repair; chromosome stability; DNA double-strand break repair; protein S-acylation; Rif1
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Research Centres and Groups: Genome Damage and Stability Centre
Depositing User: Ulrich Rass
Date Deposited: 11 Jun 2019 07:22
Last Modified: 01 Jul 2019 13:01
URI: http://sro.sussex.ac.uk/id/eprint/84215

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