CarrDNARepair.pdf (4.72 MB)
The conserved Fanconi anemia nuclease Fan1 and the SUMO E3 ligase Pli1 act in two novel Pso2-independent pathways of DNA interstrand crosslink repair in yeast
journal contribution
posted on 2023-06-08, 18:16 authored by Y Fontebasso, Thomas Etheridge, Antony OliverAntony Oliver, Jo Murray, Antony CarrAntony CarrDNA interstrand cross-links (ICLs) represent a physical barrier to the progression of cellular machinery involved in DNA metabolism. Thus, this type of adduct represents a serious threat to genomic stability and as such, several DNA repair pathways have evolved in both higher and lower eukaryotes to identify this type of damage and restore the integrity of the genetic material. Human cells possess a specialized ICL-repair system, the Fanconi anemia (FA) pathway. Conversely yeasts rely on the concerted action of several DNA repair systems. Recent work in higher eukaryotes identified and characterized a novel conserved FA component, FAN1 (Fanconi anemia-associated nuclease 1, or FANCD2/FANCI-associated nuclease 1). In this study, we characterize Fan1 in the yeast Schizosaccharomyces pombe. Using standard genetics, we demonstrate that Fan1 is a key component of a previously unidentified ICL-resolution pathway. Using high-throughput synthetic genetic arrays, we also demonstrate the existence of a third pathway of ICL repair, dependent on the SUMO E3 ligase Pli1. Finally, using sequence-threaded homology models, we predict and validate key residues essential for Fan1 activity in ICL repair.
Funding
Single Molecule Imaging of the DNA Damage Response in Live Cells; G0250; EUROPEAN UNION; 268788
Replication fork stability and fork restart; G0745; MRC-MEDICAL RESEARCH COUNCIL; G1100074-E01/1
History
Publication status
- Published
File Version
- Published version
Journal
DNA RepairISSN
15687864Publisher
ElsevierExternal DOI
Issue
12Volume
12Page range
1011-1023Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2014-09-11First Open Access (FOA) Date
2014-09-11First Compliant Deposit (FCD) Date
2014-09-11Usage metrics
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