A5051825555- DNA Repair Mechanisms
- Cancer Genomics and Diagnostics
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Fungal and yeast genetics research
- Genetic factors in colorectal cancer
- Cytomegalovirus and herpesvirus research
- Prion Diseases and Protein Misfolding
- Bacterial Genetics and Biotechnology
- RNA regulation and disease
- Heat shock proteins research
- Evolution and Genetic Dynamics
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Animal Genetics and Reproduction
- Carcinogens and Genotoxicity Assessment
- Genomics and Phylogenetic Studies
- Bacteriophages and microbial interactions
- Genetics and Neurodevelopmental Disorders
- Multiple Myeloma Research and Treatments
- Biochemical and Molecular Research
- Cancer Mechanisms and Therapy
- Fermentation and Sensory Analysis
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Protein Degradation and Inhibitors
University of California, Davis
2017-2023
University of Nebraska Medical Center
2011-2017
Nebraska Medical Center
2010-2014
C3J Therapeutics (United States)
2012
Brewster Place
2012
St Petersburg University
2007-2010
Abstract Clusters of localized hypermutation in human breast cancer genomes, named “kataegis” (from the Greek for thunderstorm), are hypothesized to result from multiple cytosine deaminations catalyzed by AID/APOBEC proteins. However, a direct link between APOBECs and kataegis is still lacking. We have sequenced genomes yeast mutants induced diploids expression gene PmCDA1, hypermutagenic deaminase sea lamprey. Analysis distribution 5,138 mutations revealed clusters very similar those found...
Genetic information should be accurately transmitted from cell to cell; conversely, the adaptation in evolution and disease is fueled by mutations. In case of cancer development, multiple genetic changes happen somatic diploid cells. Most classic studies molecular mechanisms mutagenesis have been performed haploids. We demonstrate that parameters mutation process are different populations. The genomes drug-resistant mutants induced yeast diploids base analog 6-hydroxylaminopurine (HAP) or...
Mutations in genomes of species are frequently distributed non-randomly, resulting mutation clusters, including recently discovered kataegis tumors. DNA editing deaminases play the prominent role etiology these mutations. To gain insight into enigmatic mechanisms localized hypermutagenesis that lead to cluster formation, we analyzed mutational single nucleotide variations (SNV) data obtained by whole-genome sequencing drug-resistant mutants induced yeast diploids AID/APOBEC deaminase and...
DNA polymerase (pol) η is a specialized error-prone with at least two quite different and contrasting cellular roles: to mitigate the genetic consequences of solar UV irradiation, promote somatic hypermutation in variable regions immunoglobulin genes. Misregulation mistargeting pol can compromise genome integrity. We explored whether mutational signature could be found datasets human mutations derived from normal cancer cells. A substantial excess single tandem within known mutable motifs...
Abstract Follicular lymphoma (FL) is an uncurable cancer characterized by progressive severity of relapses. We analyzed sequence context specificity mutations in the B cells from a large cohort FL patients. revealed substantial excess within novel hybrid nucleotide motif: signature somatic hypermutation (SHM) enzyme, Activation Induced Deaminase (AID), which overlaps CpG methylation site. This finding implies that SHM machinery acts at genomic sites containing methylated cytosine. identified...
Background Editing deaminases have a pivotal role in cellular physiology. A notable member of this superfamily, APOBEC3G (A3G), restricts retroviruses, and Activation Induced Deaminase (AID) generates antibody diversity by localized deamination cytosines DNA. Unconstrained deaminase activity can cause genome-wide mutagenesis cancer. The mechanisms that protect the genomic DNA from undesired action are unknown. Using vitro assays expression A3G yeast, we show replication protein (RPA),...
Cancer genomes accumulate nucleotide sequence variations that number in the tens of thousands per genome. A prominent fraction these mutations is thought to arise as a consequence off-target activity DNA/RNA editing cytosine deaminases. These enzymes, collectively called activation induced deaminase (AID)/APOBECs, deaminate cytosines located within defined DNA contexts. The resulting changes original C:G pair contexts (mutational signatures) provide indirect evidence for participation...
Abstract Current eukaryotic replication models postulate that leading and lagging DNA strands are replicated predominantly by dedicated polymerases. The catalytic subunit of the strand polymerase ε, Pol2, consists two halves made different ancestral B-family Counterintuitively, catalytically active N-terminal half is dispensable, while inactive C-terminal part required for viability. Despite extensive studies yeast Saccharomyces cerevisiae strains lacking half, it still unclear how these...
DNA editing deaminases (APOBECs) are implicated in generation of mutations somatic cells during tumorigenesis. APOBEC-dependent mutagenesis is thought to occur transient exposure unprotected single-stranded DNA. Mutations frequently clusters (kataegis). We investigated mechanisms mutant growing and resting diploid yeast expressing APOBEC from sea lamprey, PmCDA1, whose kataegistic effect was previously shown be associated with transcription. have found that the frequency canavanine-resistant...
Cancer genomes harbor numerous genomic alterations and many cancers accumulate thousands of nucleotide sequence variations. A prominent fraction these mutations arises as a consequence the off-target activity DNA/RNA editing cytosine deaminases followed by replication/repair edited sites DNA polymerases (pol), deduced from analysis context in different tumor tissues. We have used weight matrix (sequence profile) approach to analyze mutagenesis due Activation Induced Deaminase (AID) two...
Baker’s yeast, S. cerevisiae, is an excellent model organism exploited for molecular genetic studies of the mechanisms genome stability in eukaryotes. Genetic peculiarities commonly used yeast strains impact processes DNA replication, repair, and recombination (RRR). We compared genomic sequence variation five that are intensively RRR studies. next-generation sequencing data to detect extent significance 183 genes. present a detailed analysis differences were found even closely related...
Abstract DNA polymerase ε (pol ε) participates in the leading strand synthesis eukaryotes. The catalytic subunit of this enzyme, Pol2, is a fusion two ancestral B-family polymerases. Paradoxically, catalytically active N-terminal pol dispensable, and an inactive C-terminal essential for yeast cell viability. Despite extensive studies strains without half (mutation pol2-16 ), it still unclear how they survive what mechanism rapid recovery initially miserably growing cells. reason slow...