A5053258867- Fungal and yeast genetics research
- DNA Repair Mechanisms
- Carcinogens and Genotoxicity Assessment
- CRISPR and Genetic Engineering
- Metalloenzymes and iron-sulfur proteins
- RNA modifications and cancer
- Biochemical and Molecular Research
- Plant Virus Research Studies
- Plant tissue culture and regeneration
- RNA and protein synthesis mechanisms
- Chromosomal and Genetic Variations
- Adenosine and Purinergic Signaling
- DNA and Nucleic Acid Chemistry
- Epigenetics and DNA Methylation
- Plant Disease Resistance and Genetics
- Bacterial Genetics and Biotechnology
- Plant and Fungal Interactions Research
- Fungal Plant Pathogen Control
- Fermentation and Sensory Analysis
- Cancer-related gene regulation
- Electrocatalysts for Energy Conversion
- RNA regulation and disease
- Porphyrin Metabolism and Disorders
- Transgenic Plants and Applications
- Microtubule and mitosis dynamics
Baylor College of Medicine
2025
Duke University
2013-2024
Duke University Hospital
2011-2023
Duke Medical Center
2011-2023
Institut Curie
2003-2021
Université Paris Sciences et Lettres
2021
National Institute of Environmental Health Sciences
2006-2019
Triangle
2019
National Institutes of Health
2010
St Petersburg University
1996-2009
Saccharomyces cerevisiae , a well-established model for species as diverse humans and pathogenic fungi, is more recently population quantitative genetics. S. found in multiple environments—one of which the human body—as an opportunistic pathogen. To aid understanding genetics, well its emergence pathogen, we sequenced, de novo assembled, extensively manually edited annotated genomes 93 strains from geographic environmental origins, including many clinical origin strains. These strains, are...
UVA (320-400 nm) radiation constitutes >90% of the environmentally relevant solar UV radiation, and it has been proposed to have a role in skin cancer aging. Because popularity tanning beds prolonged periods sunbathing, potential deleterious effect emerged as source concern for public health. Although generally accepted, impact DNA damage on cytotoxic, mutagenic, carcinogenic remains unclear. In present study, we investigated sensitivity panel yeast mutants affected processing lethal...
We have shown previously that lack of molybdenum cofactor (MoCo) in Escherichia coli leads to hypersensitivity the mutagenic and toxic effects N-hydroxylated base analogues, such as 6-N-hydroxylaminopurine (HAP). However, nature MoCo-dependent mechanism is unknown, inactivation all known putative E. molybdoenzymes does not produce any sensitivity. Presently, we report on isolation characterization two novel HAP-hypersensitive mutants carrying defects ycbX or yiiM open reading frames. Genetic...
It has been stipulated that repair of clustered DNA lesions may be compromised, possibly leading to the formation double-strand breaks (DSB) and, thus, deleterious events. Using a variety model multiply damaged sites (MDS), we investigated parameters govern DSB during processing MDS. Duplexes carrying MDS were inserted into replicative or integrative vectors, and used transform yeast Saccharomyces cerevisiae. Formation was assessed by relevant plasmid survival assay. Kinetics...
An important issue in genome evolution is the mechanism by which tandem duplications are generated from single-copy genes. In yeast Saccharomyces cerevisiae, most strains contain tandemly duplicated copies of CUP1, a gene that encodes copper-binding metallothionein. By screening 101 natural isolates S. we identified five different types CUP1-containing repeats, as well only had one copy CUP1. A comparison DNA sequences these indicates CUP1 arrays were unequal nonhomologous recombination events gene.
Sunlight causes lesions in DNA that if unrepaired and inaccurately replicated by polymerases yield mutations result skin cancer humans. Two enzymes involved translesion synthesis (TLS) of UV-induced photolesions are polymerase eta (Poleta) zeta (Polzeta), encoded the RAD30A REV3 genes, respectively. Previous studies have investigated TLS roles these human yeast cells irradiated with monochromatic, short wavelength UVC radiation (254 nm). However, less is known about cellular responses to...
Abstract We characterized previously identified RNA viruses (L-A, L-BC, 20S, and 23S), L-A–dependent M satellites (M1, M2, M28, Mlus), satellite–dependent killer phenotypes in the Saccharomyces cerevisiae 100-genomes genetic resource population. L-BC was present all strains, albeit 2 distinct levels, L-BChi L-BClo; level is associated with genotype. L-BChi, L-A, 23S, M1, Mlus (M28 absent) were fewer strains than similarly inherited 2µ plasmid. Novel identified. Ten M+ exhibited killing (K+)...
The ham1 mutant of yeast Saccharomyces cerevisiae is sensitive to the mutagenic and lethal effects base analog, 6-N-hydroxylaminopurine (HAP). We have isolated a clone from centromere-plasmid-based genomic library complementing HAP sensitivity strain. After subcloning, 3·4 kb functional fragment was sequenced. It contained three open reading frames (ORFs) corresponding proteins 353, 197 184 amino acids long. LEU2+ disruptions promoter N-terminal part gene coding long protein led moderate...
The ham1 mutant of yeast Saccharomyces cerevisiae is sensitive to the mutagenic and lethal effects base analog, 6-N-hydroxylaminopurine (HAP). We have isolated a clone from centromere-plasmid-based genomic library complementing HAP sensitivity strain. After subcloning, 3.4 kb functional fragment was sequenced. It contained three open reading frames (ORFs) corresponding proteins 353, 197 184 amino acids long. LEU2+ disruptions promoter N-terminal part gene coding long protein led moderate...
Following the irradiation of nondividing yeast cells with ultraviolet (UV) light, most induced mutations are inherited by both daughter cells, indicating that complementary changes introduced into strands duplex DNA prior to replication. Early analyses demonstrated such two-strand depend on functional nucleotide excision repair (NER), but molecular mechanism this unique type mutagenesis has not been further explored. In experiments reported here, an ade2 adeX colony-color system was used...
ABSTRACT We have previously described a novel Escherichia coli detoxification system for the removal of toxic and mutagenic N-hydroxylated nucleobases related compounds that requires molybdenum cofactor. Two subpathways ( ycbX yiiM ) were identified, each employing molybdo activity capable inactivating by reduction to corresponding amine. In present study, we identify cysJ gene product as one additional component this system. While CysJ protein has been identified NADPH:flavin oxidoreductase...
We determined that extrachromosomal 2μ plasmid was present in 67 of the Saccharomyces cerevisiae 100-genome strains; addition to variation size and copy number 2μ, we identified three distinct classes 2μ. presence/absence class associations with populations, clinical origin nuclear genotypes. also screened genome sequences S. paradoxus, kudriavzevii, uvarum, eubayanus, mikatae, arboricolus bayanus strains for both integrated Similar cerevisiae, found no any paradoxus strains. However, part...
Chromosomes with two centromeres provide a unique opportunity to study chromosome breakage and DNA repair using completely endogenous cellular machinery. Using conditional transcriptional promoter control the second centromere, we are able activate dicentric follow appearance of products. We find that rate products resulting from homology-based mechanisms exceeds expected based on their limited centromere homology (340 bp) distance one another (up 46.3 kb). In order identify whether breaks...
ABSTRACT We have shown previously that Escherichia coli and Salmonella enterica serovar Typhimurium strains carrying a deletion of the uvrB-bio region are hypersensitive to mutagenic toxic action 6-hydroxylaminopurine (HAP) related base analogs. This sensitivity is not due uvrB excision repair defect associated with this because point mutation or uvrA deficiency does cause hypersensitivity. In present work, we investigated which gene(s) within deleted may be responsible for effect. Using...
Abstract Background N -hydroxylated base analogs, such as 6-hydroxylaminopurine (HAP) and 2-amino-6-hydroxylaminopurine (AHA), are strong mutagens in various organisms due to their ambiguous base-pairing properties. The systems protecting cells from HAP related noncanonical purines Escherichia coli include specialized deoxyribonucleoside triphosphatase RdgB, DNA repair endonuclease V, a molybdenum cofactor-dependent system. Fewer HAP-detoxification have been identified yeast Saccharomyces...
The base analogs 6-N-hydroxylaminopurine (HAP) and 2-amino-HAP (AHAP) are potent mutagens in bacteria eukaryotic organisms. Previously, we demonstrated that a defect the Escherichia coli ycbX gene, encoding molybdenum cofactor-dependent oxidoreductase, dramatically enhances sensitivity to toxic mutagenic action of these agents. In present study, describe discovery properties novel suppressor locus, yjcD, strongly reduces HAP strain. Suppressor effects also observed for other purine analogs,...
Abstract Mitochondrial genome variation and its effects on phenotypes have been widely analyzed in higher eukaryotes but less so the model eukaryote Saccharomyces cerevisiae. Here, we describe mitochondrial 96 diverse S. cerevisiae strains assess associations between genotype as well nuclear-mitochondrial epistasis. We associate sensitivity to ATP synthase inhibitor oligomycin with SNPs mitochondrially encoded ATP6 gene. use of iso-nuclear F1 pairs, equivalent reciprocal hemizygosity...
Abstract Although fusions between the centromeres of different human chromosomes have been observed cytologically in cancer cells, since are long arrays satellite sequences, details these difficult to investigate. We developed methods detecting recombination within yeast Saccharomyces cerevisiae (intercentromere recombination). These events occur at similar rates (about 10−8/cell division) two active or inactive centromeres. mapped breakpoints most a region 43 base pairs uninterrupted...
Abstract Near the C-terminus of histone H2A in yeast S. cerevisiae, there are two serines (S122 and S129) that targets phosphorylation. The phosphorylation Serine 129 response to DNA damage is dependent on Tel1 Mec1 kinases. In pombe 122 Bub1 kinase, strains with an alanine mutation this serine have elevated levels lagging chromosomes mitosis. Strains lack both cerevisiae very rates non-disjunction. To clarify functional importance H2A, we measured chromosome loss single mutant double...
The structure of human inosine triphosphate pyrophosphohydrolase (ITPA) has been determined using diffraction data to 1.6 Å resolution. ITPA contributes the accurate replication DNA by cleansing cellular dNTP pools mutagenic nucleotide purine analogs such as dITP or dXTP. A similar high-resolution unpublished deposited in Protein Data Bank from a monoclinic and pseudo-merohedrally twinned crystal. Here, cocrystallization with molar ratio XTP appears have improved crystals eliminating...