A5022253764- DNA Repair Mechanisms
- Genetic factors in colorectal cancer
- Fungal and yeast genetics research
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- RNA modifications and cancer
- Carcinogens and Genotoxicity Assessment
- Cancer Genomics and Diagnostics
- Bacterial Genetics and Biotechnology
- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- Peptidase Inhibition and Analysis
- DNA and Nucleic Acid Chemistry
- PARP inhibition in cancer therapy
- 14-3-3 protein interactions
- Chromosomal and Genetic Variations
- Blood properties and coagulation
- Ubiquitin and proteasome pathways
- Protist diversity and phylogeny
- Erythrocyte Function and Pathophysiology
- Light effects on plants
- Chronic Lymphocytic Leukemia Research
- Prion Diseases and Protein Misfolding
- Platelet Disorders and Treatments
- Metal-Catalyzed Oxygenation Mechanisms
University of Cambridge
2018-2022
Bangor University
2005-2018
Medical Research Council
2018
Cancer Research UK
2018
University of Copenhagen
2004-2017
Imperial College London
2016
University of Sussex
2005
University of Bern
1994-2004
University of Zurich
2001-2004
Technische Universität Braunschweig
1990-1995
The human UV-damaged DNA-binding protein Ddb1 associates with cullin 4 ubiquitin ligases implicated in nucleotide excision repair (NER). These complexes also contain the signalosome (CSN), but NER-relevant ubiquitination targets have not yet been identified. We report that fission yeast Ddb1, Cullin (Pcu4), and CSN subunits Csn1 Csn2 are required for degradation of ribonucleotide reductase (RNR) inhibitor Spd1. Ddb1-deficient cells >20-fold increased spontaneous mutation rate. This is...
Summary Plants are unique in the obligatory nature of their exposure to sunlight and consequently ultraviolet (UV) irradiation. However, our understanding plant DNA repair processes lags far behind current knowledge mechanisms microbes, yeast mammals, especially concerning universally conserved versatile dark pathway called nucleotide excision (NER). Here we report isolation functional characterization Arabidopsis thaliana AtRAD1 , which encodes homologue Saccharomyces cerevisiae RAD1,...
Nucleotide synthesis is a universal response to DNA damage, but how this facilitates repair and cell survival unclear. Here we establish role for damage-induced nucleotide in homologous recombination (HR) fission yeast. Using genetic screen, found the Ddb1–Cul4 Cdt2 ubiquitin ligase complex ribonucleotide reductase (RNR) be required HR of double-strand break (DSB). The degradation Spd1, an inhibitor RNR Accordingly, deleting spd1 + suppressed damage sensitivity reduced efficiency associated...
The correct levels of deoxyribonucleotide triphosphates and their relative abundance are important to maintain genomic integrity. Ribonucleotide reductase (RNR) regulation is complex multifaceted. RNR regulated allosterically by two nucleotide-binding sites, transcriptional control, small inhibitory proteins that associate with the R1 catalytic subunit. In addition, subcellular localization R2 subunit through cell cycle in response DNA damage. We show fission yeast inhibitor Spd1...
Journal Article The swi4+ gene of Schizosaccharomyces pombe encodes a homologue mismatch repair enzymes Get access Oliver Fleck, Fleck Search for other works by this author on: Oxford Academic PubMed Google Scholar Holger Michael, Michael Lutz Heim 1Max-Planck-Institut für Biophysikalische ChemieAm Fassberg, W-3400 Göttingen, Germany Nucleic Acids Research, Volume 20, Issue 9, 11 May 1992, Pages 2271–2278, https://doi.org/10.1093/nar/20.9.2271 Published: 1992 history Received: 04 February...
We have identified in the fission yeast Schizosaccharomyces pombe a MutS homolog that shows highest homology to Msh2 subgroup. msh2 disruption gives rise increased mitotic mutation rates and levels of postmeiotic segregation genetic markers. In bandshift assays performed with msh2Delta cell extracts, general mismatch-binding activity is absent. By complementation assays, we showed S. allelic previously swi8 mut3 genes, which are involved mating-type switching. The swi8-137 mutant has gene...
Cullin4, Ddb1 and Cdt2 are core subunits of the ubiquitin ligase complex CRL4(Cdt2), which controls genome stability by targeting Spd1 for degradation during DNA replication repair in fission yeast. has an inhibitory effect on ribonucleotide reductase (RNR), activity is required deoxynucleotide (dNTP) synthesis. The failure to degrade mutants where CRL4(Cdt2) defective leads integrity checkpoint activation dependency. This correlates with a lower dNTP pool. Pools restored spd1-deleted...
In yeasts, small intrinsically disordered proteins (IDPs) modulate ribonucleotide reductase (RNR) activity to ensure an optimal supply of dNTPs for DNA synthesis. The S. pombe Spd1 protein can directly inhibit the large RNR subunit (R1), import (R2) into nucleus and induce architectural change in R1-R2 holocomplex. Here, we report characterization Spd2, a with homology Spd1. We show that Spd2 is CRL4Cdt2 controlled IDP functions together damage response modulation architecture. However, does...
The mismatch-binding activity Cmb1 of Schizosaccharomyces pombe was enriched from wild type cells, and N-terminal sequencing enabled cloning the respective gene. deduced amino acid sequence cmb1 +contains a high mobility group domain, motif that is common to heterogeneous family DNA-binding proteins. In crude protein extracts gene-disruption strain, specific binding C/T, C/A, C/Δ abolished. Weak C/C revealed presence second activity, Cmb2. Cmb1, fromS. purified Escherichia coli,bound...
Abstract The mismatch repair (MMR) system ensures genome integrity by removing mispaired and unpaired bases that originate during replication. A major source of mutational changes is strand slippage in repetitive DNA sequences without concomitant repair. We established a genetic assay allows measuring the stability GT repeats ade6 gene Schizosaccharomyces pombe. In repair-proficient strains most repeat variations were insertions, with addition two nucleotides being frequent event. highly...
Abstract The msh6 mismatch repair gene of Schizosaccharomyces pombe was cloned, sequenced, and inactivated. Strains bearing all combinations inactivated msh6, msh2, swi4 (the S. MSH3 ortholog) alleles were tested for their defects in mitotic meiotic repair. Mitotic mutation rates similarly increased msh2 mutants, both reversion a base-base substitution as well an insertion one nucleotide mononucleotide run. Tetrad analysis intragenic two-factor crosses revealed that affected to the same...
Efficient protein synthesis in eukaryotes requires diphthamide modification of translation elongation factor eEF2 and wobble uridine modifications tRNAs. In higher eukaryotes, these processes are important for preventing neurological developmental defects cancer. this study, we used Schizosaccharomyces pombe as a model to analyse mutants defective (dph1Δ), tRNA (elp3Δ), or both (dph3Δ) sensitivity cytotoxic agents thermal stress. The dph3Δ elp3Δ were sensitive range drugs had growth at low...
Abstract Rhp41 and Rhp42 of Schizosaccharomyces pombe are homologues human XPC, which is involved in nucleotide excision repair (NER) damaged DNA. Inactivation rhp41 caused moderate sensitivity to ultraviolet (UV) radiation. In addition, an increase mitotic mutation rates was observed the mutant, dependent on active translesion polymerase Z. UV were not different between rhp42 wild type, but compared further increased cells. Transcription fbp1 gene (induced vegetative cells) SPBC1289.14...