A5000953325- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- PARP inhibition in cancer therapy
- Evolution and Genetic Dynamics
- Cancer Genomics and Diagnostics
- Effects of Radiation Exposure
- Cancer therapeutics and mechanisms
- DNA and Nucleic Acid Chemistry
- Gene Regulatory Network Analysis
- Fungal and yeast genetics research
- Pluripotent Stem Cells Research
- Genomics and Phylogenetic Studies
- Microbial Metabolic Engineering and Bioproduction
- RNA Research and Splicing
- Bioinformatics and Genomic Networks
- Plant tissue culture and regeneration
- Chromosomal and Genetic Variations
- Genetics, Aging, and Longevity in Model Organisms
- Glutathione Transferases and Polymorphisms
- Genomics and Chromatin Dynamics
- Plant Genetic and Mutation Studies
- Telomeres, Telomerase, and Senescence
- Ubiquitin and proteasome pathways
Wellcome Sanger Institute
2015-2021
University of Cambridge
2015-2021
The Gurdon Institute
2015-2021
Wellcome Trust
2016-2019
University of California, Berkeley
2016
Mutations in the ATM tumor suppressor gene confer hypersensitivity to DNA-damaging chemotherapeutic agents. To explore genetic resistance mechanisms, we performed genome-wide CRISPR-Cas9 screens cells treated with DNA topoisomerase I inhibitor topotecan. Thus, here establish that inactivating terminal components of non-homologous end-joining (NHEJ) machinery or BRCA1-A complex specifically topotecan ATM-deficient cells. We show ATM-mutant poly-(ADP-ribose) polymerase (PARP) olaparib reflects...
Article21 April 2015Open Access Synthetic viability genomic screening defines Sae2 function in DNA repair Fabio Puddu The Gurdon Institute and Department of Biochemistry, University Cambridge, UK Search for more papers by this author Tobias Oelschlaegel Ilaria Guerini Nicola J Geisler Hengyao Niu Molecular Biophysics Yale School Medicine, New Haven, CT, USA Mareike Herzog Wellcome Trust Sanger Institute, Hinxton, Israel Salguero Bernardo Ochoa-Montaño Emmanuelle Viré Patrick Sung David Adams...
The organization of the genome is nonrandom and important for correct function. Specifically, nuclear envelope plays a critical role in gene regulation. It generally constitutes repressive environment, but several genes, including GAL locus budding yeast, are recruited to periphery on activation. Here, we combine imaging computational modeling ask how association single with influences surrounding chromosome architecture. Systematic analysis an entire yeast establishes that peripheral...
Significance Deficiencies in genome maintenance genes result increased mutagenesis and rearrangements that impact cell viability, species adaptation, evolvability. The accumulation of somatic mutations is also a landmark most tumor cells but it remains difficult to retrospectively determine their mechanistic origin(s). Here, we conducted prospective reciprocal approach inactivate evolutionary conserved involved various processes characterize de novo diploid S. cerevisiae mutation lines. Our...
Over the past decades, there have been huge advances in understanding cellular responses to ionising radiation (IR) and DNA damage. These studies, however, were mostly executed with cell lines mice using single or multiple acute doses of radiation. Hence, relatively little is known about how continuous exposure low dose affects normal cells organisms, even though our are constantly exposed levels We addressed this issue by examining consequences exposing human primary γ-radiation delivered...
Abstract A single amino acid residue change in the exonuclease domain of human DNA polymerase ϵ, P286R, is associated with development colorectal cancers, and has been shown to impart a mutator phenotype. The corresponding Pol ϵ allele yeast Saccharomyces cerevisiae (pol2-P301R), was found drive greater mutagenesis than an entirely exonuclease-deficient (pol2–4), unexpected phenotype ultra-mutagenesis. By studying impact on mutation frequency, type, replication-strand bias, sequence context,...
Abstract Camptothecin‐induced locking of topoisomerase 1 on DNA generates a physical barrier to replication fork progression and creates topological stress. By allowing replisome rotation, absence the Tof1/Csm3 complex promotes conversion impending stress catenation causes camptothecin hypersensitivity. Through synthetic viability screening, we discovered that histone H4 K16 deacetylation drives sensitivity yeast cells inactivation this pathway by mutating or genes SIR 1‐4 suppresses much...
Establishing genetic and chemo-genetic interactions has played key roles in elucidating mechanisms by which certain chemicals perturb cellular functions. In contrast to gene disruption/depletion strategies identify of drug resistance, searching for point-mutational suppressors that can separation- or gain-of-function mutations been limited. Here, demonstrating its utility identifying chemical-genetic sensitivity the DNA topoisomerase I poison camptothecin poly(ADP-ribose) polymerase...
Summary Mutations in the ATM tumor suppressor confer hypersensitivity to DNA-damaging agents. To explore genetic resistance mechanisms, we performed genome-wide CRISPR-Cas9 screens cells treated with DNA topoisomerase poison topotecan. Thus, establish that loss of terminal components non-homologous end-joining (NHEJ) machinery or BRCA1-A complex specifically confers topotecan ATM-deficient cells. We show ATM-mutant poly-(ADP-ribose) polymerase inhibitor olaparib is due delayed homologous...
Over the past decades, there have been huge advances in understanding cellular responses to ionising radiation (IR) and DNA damage. These studies, however, were mostly executed with cell lines mice using single or multiple acute doses of radiation. Hence, relatively little is known about how continuous exposure low dose affects normal cells organisms, even though our are constantly exposed levels We addressed this issue by examining consequences exposing human primary γ-radiation delivered...
ABSTRACT A single amino acid residue change in the exonuclease domain of human DNA polymerase ε, P286R, is associated with development colorectal cancers, and has been shown to impart a mutagenic phenotype. Perhaps unexpectedly, corresponding Pol ε allele yeast Saccharomyces cerevisiae ( pol2-P301R ), was found drive greater mutagenesis than exonuclease-deficient pol2-4 phenotype sometimes termed ultra -mutagenesis. By studying impact on mutation frequency, type, replication-strand bias,...
ABSTRACT Genetic and chemo-genetic interactions have played key roles in elucidating the molecular mechanisms by which certain chemicals perturb cellular functions. Many studies employed gene knockout collections or disruption/depletion strategies to identify routes for evolving resistance chemical agents. By contrast, searching point-mutational genetic suppressors that can separation- gain-of-function mutations, has been limited even simpler, genetically amenable organisms such as yeast,...