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

Fontebasso, Y, Etheridge, T J, Oliver, A W, Murray, J M and Carr, A M (2013) 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. DNA Repair, 12 (12). pp. 1011-1023. ISSN 15687864

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Abstract

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.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: R Medicine > R Medicine (General)
Depositing User: Catrina Hey
Date Deposited: 11 Sep 2014 11:02
Last Modified: 07 Mar 2017 07:42
URI: http://sro.sussex.ac.uk/id/eprint/49894

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Project NameSussex Project NumberFunderFunder Ref
Single Molecule Imaging of the DNA Damage Response in Live CellsG0250EUROPEAN UNION268788
Replication fork stability and fork restartG0745MRC-MEDICAL RESEARCH COUNCILG1100074-E01/1