Fontana_et_al-2019-Nature_Communications.pdf (2.1 MB)
Rif1 S-acylation mediates DNA double-strand break repair at the inner nuclear membrane
journal contribution
posted on 2023-06-09, 18:02 authored by Gabriele A Fontana, Daniel Hess, Julia K Reinert, Stefano Mattarocci, Benoît Falquet, Dominique Klein, David Shore, Nicolas H Thoma¨, Ulrich RassUlrich RassRif1 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.
History
Publication status
- Published
File Version
- Published version
Journal
Nature CommunicationsISSN
2041-1723Publisher
Nature ResearchExternal DOI
Issue
2535Volume
10Page range
1-14Department 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
2019-06-11First Open Access (FOA) Date
2019-06-11First Compliant Deposit (FCD) Date
2019-06-10Usage metrics
Categories
No categories selectedLicence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC