Details

Autor(en) / Beteiligte

• Fontana, Gabriele A
• Hess, Daniel
• Reinert, Julia K
• Mattarocci, Stefano
• Falquet, Benoît
• Klein, Dominique
• Shore, David
• Thomä, Nicolas H
• Rass, Ulrich

Titel

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

Ist Teil von

• Nature communications, 2019-06, Vol.10 (1), p.2535-2535, Article 2535

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.