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Deletion of ULS1 confers damage tolerance in sgs1 mutants through a Top3-dependent D-loop mediated fork restart pathway
- Source :
- DNA repair. 78
- Publication Year :
- 2019
-
Abstract
- Homologous recombination (HR)-based repair during DNA replication can apparently utilize several partially overlapping repair pathways in response to any given lesion. A key player in HR repair is the Sgs1-Top3-Rmi1 (STR) complex, which is critical for resolving X-shaped recombination intermediates formed following bypass of methyl methanesulfonate (MMS)-induced damage. STR mutants are also sensitive to the ribonucleotide reductase inhibitor, hydroxyurea (HU), but unlike MMS treatment, HU treatment is not accompanied by X-structure accumulation, and it is thus unclear how STR functions in this context. Here we provide evidence that HU-induced fork stalling enlists Top3 prior to recombination intermediate formation. The resistance of sgs1Δ mutants to HU is enhanced by the absence of the putative SUMO (Small Ubiquitin MOdifier)-targeted ubiquitin ligase, Uls1, and we demonstrate that Top3 is required for this enhanced resistance and for coordinated breaks and subsequent d-loop formation at forks stalled at the ribosomal DNA (rDNA) replication fork block (RFB). We also find that HU resistance depends on the catalytic activity of the E3 SUMO ligase, Mms21, and includes a rapid Rad51-dependent restart mechanism that is different from the slow Rad51-independent HR fork restart mechanism operative in sgs1Δ ULS1+ mutants. These data support a model in which repair of HU-induced damage in sgs1Δ mutants involves an error-prone break-induced replication pathway but, in the absence of Uls1, shifts to one that is higher-fidelity and involves the formation of Rad51-dependent d-loops.
- Subjects :
- DNA Replication
Saccharomyces cerevisiae Proteins
Mutant
Context (language use)
Saccharomyces cerevisiae
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Ubiquitin
Homologous Recombination
Molecular Biology
030304 developmental biology
0303 health sciences
biology
RecQ Helicases
DNA replication
DNA Helicases
Cell Biology
Methyl methanesulfonate
Ubiquitin ligase
Cell biology
chemistry
030220 oncology & carcinogenesis
biology.protein
Homologous recombination
Gene Deletion
Sgs1
Subjects
Details
- ISSN :
- 15687856
- Volume :
- 78
- Database :
- OpenAIRE
- Journal :
- DNA repair
- Accession number :
- edsair.doi.dedup.....b94e3431aa1e162684488cd7ccfe8d3c