Publications by authors named "James P Wells"

Article Synopsis
  • ARID1A, a key part of the BAF chromatin remodeling complex and mutated in about 8% of cancers, shows highest mutation rates in clear cell ovarian carcinoma (CCOC), reaching over 50%.
  • Current treatments for ARID1A-deficient cancers are limited, prompting research into genetic dependencies using CRISPR screening.
  • The study identifies KEAP1 as a critical factor in ARID1A-deficient cells, where targeting KEAP1 leads to selective growth inhibition and worsens genome instability, highlighting a potential new therapeutic approach.
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DNA replication is a vulnerable time for genome stability maintenance. Intrinsic stressors, as well as oncogenic stress, can challenge replication by fostering conflicts with transcription and stabilizing DNA:RNA hybrids. RAD18 is an E3 ubiquitin ligase for PCNA that is involved in coordinating DNA damage tolerance pathways to preserve genome stability during replication.

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ARID1A is a core DNA-binding subunit of the BAF chromatin remodeling complex, and is lost in up to 7% of all cancers. The frequency of ARID1A loss increases in certain cancer types, such as clear cell ovarian carcinoma where ARID1A protein is lost in about 50% of cases. While the impact of ARID1A loss on the function of the BAF chromatin remodeling complexes is likely to drive oncogenic gene expression programs in specific contexts, ARID1A also binds genome stability regulators such as ATR and TOP2.

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R loops are three-stranded nucleic acid structures consisting of an RNA molecule that has invaded duplex DNA. R-loop structures have normal functions in regulating gene expression, class-switch recombination, telomere stability, and mitochondrial DNA replication. However, unscheduled R-loop accumulation is a driver of DNA replication stress and genome instability.

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Ectopic R-loop accumulation causes DNA replication stress and genome instability. To avoid these outcomes, cells possess a range of anti-R-loop mechanisms, including RNaseH that degrades the RNA moiety in R-loops. To comprehensively identify anti-R-loop mechanisms, we performed a genome-wide trigenic interaction screen in yeast lacking RNH1 and RNH201.

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Background: Stilbene cleaving oxygenases (SCOs), also known as lignostilbene-α,β-dioxygenases (LSDs) mediate the oxidative cleavage of the olefinic double bonds of lignin-derived intermediate phenolic stilbenes, yielding small modified benzaldehyde compounds. SCOs represent one branch of the larger carotenoid cleavage oxygenases family. Here, we describe the structural and functional characterization of an SCO-like enzyme from the soil-born, bio-control agent Pseudomonas brassicacearum.

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Detailed measurements were acquired from 168 healthy subjects who were brought to the West Virginia School of Osteopathic Medicine's Robert C. Byrd Clinic in Lewisburg, WVa, during 1998 and 1999 by their parents for routine well-baby visits. Measurements of body-segment length, diameter, circumference, and skinfold thickness were taken at several segment locations.

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The collection of data on physical parameters of body segments is a preliminary critical step in studying the biomechanics of locomotion. Little data on nonhuman body segment parameters has been published. The lack of standardization of techniques for data collection and presentation has made the comparative use of these data difficult and at times impossible.

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This study examines the positional and activity behavior of a captive slow loris, Nycticebus coucang. The male individual was housed in a primate facility providing a seminatural environment and was subjected to a series of videotape recordings from which 1,878 point observations were taken. The enclosure was designed to allow maximum flexibility of substrate use.

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