Rif1 S-acylation mediates DNA double-strand break repair at the inner nuclear membrane.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31182712.
- Also identified by DOI 10.1038/s41467-019-10349-z and PMC identifier 6557901.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- DNA Breaks, Double-Stranded
- DNA End-Joining Repair
- Repressor Proteins
- Saccharomyces cerevisiae
- Saccharomyces cerevisiae Proteins
- Telomere-Binding Proteins