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Full-Text Articles in Chemistry
P62-Dependent Phase Separation Of Patient-Derived Keap1 Mutations And Nrf2, E. W. Cloer, P. F. Siesser, E. M. Cousins, D Goldfarb, D. D. Mowrey, Joseph S. Harrison, S. J. Weir, N. V. Dokholyan, M. B. Major
P62-Dependent Phase Separation Of Patient-Derived Keap1 Mutations And Nrf2, E. W. Cloer, P. F. Siesser, E. M. Cousins, D Goldfarb, D. D. Mowrey, Joseph S. Harrison, S. J. Weir, N. V. Dokholyan, M. B. Major
College of the Pacific Faculty Articles
Cancer-derived loss-of-function mutations in the KEAP1 tumor suppressor gene stabilize the NRF2 transcription factor, resulting in a pro-survival gene expression program that alters cellular metabolism and neutralizes oxidative stress. In a recent genotype-phenotype study, we classified 40% of KEAP1 mutations as ANCHOR mutants. By immunoprecipitation, these mutants bind more NRF2 than wild-type KEAP1 and ubiquitylate NRF2, but are incapable of promoting NRF2 degradation. BioID-based protein interaction studies confirmed increased abundance of NRF2 within the KEAP1 ANCHOR mutant complexes with no other statistically significant changes to the complexes. Discrete molecular dynamic simulation modeling and limited proteolysis suggest that the ANCHOR mutations …
Comparative Biochemical Analysis Of Uhrf Proteins Reveals Molecular Mechanisms That Uncouple Uhrf2 From Dna Methylation Maintenance, Robert M. Vaughan, Bradley M. Dickson, Evan M. Cornett, Joseph S. Harrison, Brian Kuhlman, Scott B. Rothbart
Comparative Biochemical Analysis Of Uhrf Proteins Reveals Molecular Mechanisms That Uncouple Uhrf2 From Dna Methylation Maintenance, Robert M. Vaughan, Bradley M. Dickson, Evan M. Cornett, Joseph S. Harrison, Brian Kuhlman, Scott B. Rothbart
College of the Pacific Faculty Articles
UHRF1 is a histone- and DNA-binding E3 ubiquitin ligase that functions with DNMT1 to maintain mammalian DNA methylation. UHRF1 facilitates DNMT1 recruitment to replicating chromatin through a coordinated mechanism involving histone and DNA recognition and histone ubiquitination. UHRF2 shares structural homology with UHRF1, but surprisingly lacks functional redundancy to facilitate DNA methylation maintenance. Molecular mechanisms uncoupling UHRF2 from DNA methylation maintenance are poorly defined. Through comprehensive and comparative biochemical analysis of recombinant human UHRF1 and UHRF2 reader and writer activities, we reveal conserved modes of histone PTM recognition but divergent DNA binding properties. While UHRF1 and UHRF2 diverge in their …
Dna Lesions Produced From The Reaction Of Diols And 5-Formylcytosine And Their Effects On Dna Replication, Brock Allen
Dna Lesions Produced From The Reaction Of Diols And 5-Formylcytosine And Their Effects On Dna Replication, Brock Allen
University of the Pacific Theses and Dissertations
Nucleic acids are complex macromolecules that are susceptible to both endogenous and exogenous damage. This study explored damage resulting from interactions with environmental nucleophilic toxins, such as a variety of diols and amines found in industry. These nucleophiles can react with electrophilic groups, such as 5-formylcytosine. 5-formylcytosine is an oxidation product of the epigenetic base 5-methylcytosine. It is typically removed by thymine DNA glycosylase (TDG) but is known to accumulate in the genome, making the formyl group susceptible to attack. In this study we used GC/MS and ESI-MS to show that DNA lesions from the nucleophilic addition reaction of toxins …