A5026001356- DNA Repair Mechanisms
- Bacterial Genetics and Biotechnology
- CRISPR and Genetic Engineering
- Evolution and Genetic Dynamics
- Nutritional Studies and Diet
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- DNA and Nucleic Acid Chemistry
- RNA and protein synthesis mechanisms
- Antibiotic Resistance in Bacteria
- Bacteriophages and microbial interactions
- Health, Environment, Cognitive Aging
- Epigenetics and DNA Methylation
- Carcinogens and Genotoxicity Assessment
- Photosynthetic Processes and Mechanisms
- Cardiovascular Disease and Adiposity
- Cancer therapeutics and mechanisms
- Genomics and Chromatin Dynamics
- Mitochondrial Function and Pathology
- Gene Regulatory Network Analysis
- Plant Genetic and Mutation Studies
- Genomics and Rare Diseases
- Mycobacterium research and diagnosis
- RNA modifications and cancer
Baylor College of Medicine
2016-2025
Rice University
2018-2023
Baylor Genetics
2013-2023
Children's Cancer Center
2007-2019
Baylor University
2018
Dan L Duncan Comprehensive Cancer Center
2014-2018
Institute of Molecular and Cell Biology
2003
University of Alberta
1991-2000
Iowa City VA Medical Center
1995
University of Oregon
1983-1991
Sewing Up DNA Repair All cells have a battery of DNA-repair pathways to help ensure genome maintenance and stability, including stress-induced break repair in Escherichia coli. Similar pathways—which can be mutagenic—are known yeast human the potential accelerate evolution. Sixteen proteins are required for pathway E. Al Mamun et al. (p. 1344 ) analyzed coli determine full complement protein contributions pathway. Ninety-three genes were found repair. One-third identified network involved...
Bacteria can rapidly evolve resistance to antibiotics via the SOS response, a state of high-activity DNA repair and mutagenesis. We explore here first steps this evolution in bacterium Escherichia coli. Induction response by genotoxic antibiotic ciprofloxacin changes E. coli rod shape into multichromosome-containing filaments. show that at subminimal inhibitory concentrations bacterial filament divides asymmetrically repeatedly tip. Chromosome-containing buds are made that, if resistant,...
Many waterbodies across the United States do not meet water quality standards. To help determine where and to what extent improvements should be sought, policymakers must consider costs of regulations with their monetized values. We ...Scientific knowledge related quantifying benefits for landscape-wide does current regulatory benefit–cost analysis needs in States. In this study we addressed gap by ...
The genetic requirements for adaptive mutation in Escherichia coli parallel those homologous recombination the recB CD pathway. Recombination-deficient recA and null mutant strains are deficient reversion. A hyper-recombinagenic recD strain is hypermutable, its hypermutation depends on functional genes. Genes of subsidiary systems not required. These results indicate that molecular mechanism by which occurs includes recombination. No such association seen spontaneous growing cells.
Adaptive reversion of a +1 frameshift mutation in Escherichia coli , which requires homologous recombination functions, is shown here to occur by -1 deletions regions small mononucleotide repeats. This pattern makes improbable recombinational mechanisms for adaptive blocks sequences are transferred into the mutating gene, and it supports that use DNA polymerase errors. The appears similar mutations found yeast cells hereditary colon cancer deficient mismatch repair. These results suggest...
Gene amplification is a collection of processes whereby DNA segment reiterated to multiple copies per genome. It important in carcinogenesis and resistance chemotherapeutic agents, can underlie adaptive evolution via increased expression an amplified gene, new gene functions, genome evolution. Though first described the model organism Escherichia coli early 1960s, only scant information on mechanism(s) this system has been obtained, many models for were possible. More recently, some...
Genomic instability underlies many cancers and generates genetic variation that drives cancer initiation, progression, therapy resistance. In contrast with classical assumptions mutations occur purely stochastically at constant, gradual rates, microbes, plants, flies, human cells possess mechanisms of mutagenesis are upregulated by stress responses. These generate transient, genetic-diversity bursts can propel evolution, specifically when poorly adapted to their environments-that is,...
Double-stranded DNA ends, often from replication, drive genomic instability, yet their origin in non-replicating cells is unknown. Here we show that transcriptional RNA/DNA hybrids (R-loops) generate ends underlie stress-induced mutation and amplification. Depleting with overproduced RNase HI reduces both changes, indicating as intermediates both. An Mfd requirement inhibition by translation implicate R-loops. R-loops promote instability generating shown dispensability when are provided...
Basic ideas about the constancy and randomness of mutagenesis that drives evolution were challenged by discovery mutation pathways activated stress responses. These could promote specifically when cells are maladapted to their environment (i.e., stressed). However, clearest example—a general stress-response–controlled switch error-prone DNA break (double-strand break, DSB) repair—was suggested be peculiar an Escherichia coli F′ conjugative plasmid, not generally significant, occur...
Spontaneous DNA breaks instigate genomic changes that fuel cancer and evolution, yet direct quantification of double-strand (DSBs) has been limited. Predominant sources spontaneous DSBs remain elusive. We report synthetic technology for quantifying using fluorescent-protein fusions end-binding protein, Gam bacteriophage Mu. In Escherichia coli GamGFP forms foci at chromosomal pinpoints their subgenomic locations. occur mostly one per cell, correspond with generations, supporting replicative...
Evolutionary theory assumed that mutations occur constantly, gradually, and randomly over time. This formulation from the "modern synthesis" of 1930s was embraced decades before molecular understanding genes or mutations. Since then, our labs others have elucidated mutation mechanisms activated by stress responses. Stress-induced produce mutations, potentially accelerating evolution, specifically when cells are maladapted to their environment, is, they stressed. The stress-induced being...
Summary Many recombination, DNA repair and replication mutants have high basal levels of SOS expression as determined by a sulAp‐lacZ reporter gene system on population cells. Two opposing models to explain how the is distributed in these cells are: (i) ‘Uniform Expression Model (UEM)’ where evenly all or (ii) ‘Two Population (TPM)’ some are highly induced while others not at all. To distinguish between two models, method quantify individual bacterial was developed fusing an promoter ( sulAp...