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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

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posted on 2023-06-08, 18:16 authored by Y Fontebasso, Thomas Etheridge, Antony OliverAntony Oliver, Jo Murray, Antony CarrAntony Carr
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.

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 Repair

ISSN

15687864

Publisher

Elsevier

Issue

12

Volume

12

Page range

1011-1023

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2014-09-11

First Open Access (FOA) Date

2014-09-11

First Compliant Deposit (FCD) Date

2014-09-11

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