A5084857431- Trypanosoma species research and implications
- Cancer Genomics and Diagnostics
- RNA regulation and disease
- Genetic factors in colorectal cancer
- RNA and protein synthesis mechanisms
- Biochemical and Molecular Research
- DNA Repair Mechanisms
- Evolution and Genetic Dynamics
- Peptidase Inhibition and Analysis
- RNA modifications and cancer
- Viral Infections and Immunology Research
Infectious Disease Research Institute
2023
Seattle Reproductive Medicine
2021
University of Washington
2019-2020
Abstract “Mutator” tumor cells that cannot correct DNA replication errors exhibit an extremely high mutation rate accelerates their evolution. But this gamble puts them at risk for extinction....
We report the properties of two mutations in exonuclease domain Saccharomyces cerevisiae DNA polymerase ϵ. One, pol2-Y473F, increases mutation rate by about 20-fold, similar to catalytically dead pol2-D290A/E290A mutant. The other, pol2-N378K, is a stronger mutator. Both retain ability excise nucleotide from double-stranded DNA, but with impaired activity. pol2-Y473F degrades poorly, while pol2-N378K single-stranded at an elevated relative DNA. These data suggest that reduces capacity enzyme...
Trypanosoma brucei and related kinetoplastid parasites possess unique RNA processing pathways, including in their mitochondria, that regulate metabolism development. Altering composition or conformation through nucleotide modifications is one such pathway, pseudouridine fate function many organisms. We surveyed synthase (PUS) orthologs trypanosomatids, with a particular interest mitochondrial enzymes due to potential importance for metabolism. (mt)-LAF3 an ortholog of human yeast PUS...
The gRNA directed U-insertion and deletion editing of mitochondrial mRNAs that is essential in different life-cycle stages for the protozoan parasite Trypanosoma brucei performed by three similar multiprotein catalytic complexes (CCs) contain requisite enzymes. These CCs also a common set eight proteins have no apparent direct function, including six an OB-fold domain. We show here one these proteins, KREPA3 (A3), has structural homology to other editing, multifunctional. investigated A3...
Abstract Each of the three similar RNA Editing Catalytic Complexes (RECCs) that perform gRNA-directed uridine insertion and deletion during Trypanosoma brucei mitochondrial (mt) mRNA editing has a distinct endonuclease activity requires two related RNase III proteins, with only one competent for catalysis. We identified multiple loss-of-function mutations in other motifs non-catalytic KREPB6, KREPB7, KREPB8 components by random mutagenesis screening. These had various effects on growth,...
Trypanosoma brucei and related kinetoplastid parasites possess unique RNA processing pathways, including in their mitochondria, that regulate metabolism development. Altering composition or conformation through nucleotide modifications is one such pathway, pseudouridine fate function many organisms. We surveyed synthase (PUS) orthologs Trypanosomatids, with a particular interest mitochondrial enzymes due to potential importance for metabolism. T. mt-LAF3 an ortholog of human yeast PUS...
The gRNA directed U-insertion and deletion editing of mitochondrial mRNAs that is essential in different life cycle stages for the protozoan parasite Trypanosoma brucei performed by three similar multi-protein catalytic complexes (CCs) contain requisite enzymes. These CCs also a common set eight proteins have no apparent direct function, including six an OB-fold domain. We show here one these proteins, KREPA3 (A3), has structural homology to other multifunctional. investigated A3 function...
Abstract Heterozygous mutations affecting DNA polymerase (Pol) exonuclease domains and homozygous inactivation of mismatch repair (MMR) each generate “mutator” phenotypes capable driving tumorigenesis. Cancers with both defects exhibit an explosive increase in mutation burden that appears to reach a threshold, consistent selection acting against further accumulation. In haploid yeast, simultaneous proofreading MMR select for “antimutator” mutants suppress the mutator phenotype. We report...