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.
Date
2013-12ICR Author
Author
Fontebasso, Y
Etheridge, TJ
Oliver, AW
Murray, JM
Carr, AM
Type
Journal Article
Metadata
Show full item recordAbstract
DNA 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.
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https://ac.els-cdn.com/S1568786413002425/1-s2.0-S1568786413002425-main.pdf?_tid=f2098b31-a780-4905-828a-98edfb825ae5&acdnat=1528458366_b0c8b54003206acde0dcc0f3fef5724cCollections
Subject
Schizosaccharomyces
DNA Damage
Esterases
Endodeoxyribonucleases
Ligases
Ubiquitin-Protein Ligases
Schizosaccharomyces pombe Proteins
Evolution, Molecular
Signal Transduction
DNA Repair
Recombination, Genetic
Protein Structure, Tertiary
Sequence Homology
Models, Molecular
High-Throughput Screening Assays
Mutation Rate
Language
eng
Date accepted
2013-10-07
License start date
2013-12
Citation
DNA repair, 2013, 12 (12), pp. 1011 - 1023