Biology subjects

Kwon, M.

Publications and source records attributed to Kwon, M..

5 recordsLinked to original sources

bioRxiv2018

Characterization of cis-prenyltransferase complexes in guayule (Parthenium argentatum), an alternative natural rubber-producing plant

Guayule (Parthenium argentatum) is a perennial shrub in the Asteraceae family and synthesizes a high quality, hypoallergenic cis-1,4-polyisoprene (or natural rubber; NR). Despite its potential to be an alternative NR supplier, the enzymes for cis-polyisoprene biosynthesis have not been comprehensively studied in guayule. Recently, implications of the protein complex involving cis-prenyltransferases (CPTs) and CPT-binding proteins (CBPs) in NR biosynthesis were shown in lettuce and dandelion, but such protein complexes have yet to be examined in guayule. Here we identified four guayule genes - three PaCPTs (PaCPT1-3) and one PaCBP, whose protein products form PaCPT/PaCBP complexes. Co-expression of both PaCBP and each of the PaCPTs could complemented the dolichol (a short cis-polyisoprene)-deficient yeast, whereas the individual expressions could not. Microsomes from the PaCPT/PaCBP-expressing yeast efficiently incorporated 14C-isopentenyl diphosphate into dehydrodolichyl diphosphates. Furthermore, co-immunoprecipitation and split-ubiquitin yeast 2-hybrid assays using PaCPTs and PaCBP confirmed the formation of protein complexes. Of the three PaCPTs, transcriptomics analysis indicated that the protein complex formed by PaCPT3 and PaCBP is likely to be the key component in guayule NR biosynthesis. The comprehensive analyses of these PaCPTs and PaCBP here provide the foundational knowledge to generate a high NR-yielding guayule.

plant biology↗

bioRxiv2018

Nuclear envelope assembly defects link mitotic errors to chromothripsis

Defects in the architecture or integrity of the nuclear envelope (NE) are associated with a variety of human diseases1. Micronuclei, one common nuclear aberration, are an origin for chromothripsis2,3, a catastrophic mutational process commonly observed in cancer genomes and other contexts4-6. Micronuclei have a defective NE, with the extensive chromosome fragmentation that generates chromothripsis occurring after abrupt, spontaneous loss of NE integrity7. After NE disruption, the exposed cytoplasmic DNA can additionally initiate proinflammatory signaling linked to senescence, metastasis, and the immune clearance of tumor cells8. Despite its broad physiological impact, the basis for the nuclear envelope fragility of micronuclei is unknown. Here we demonstrate that micronuclei undergo markedly defective NE assembly: Only \"core\" NE proteins9,10 assemble efficiently on lagging chromosomes whereas \"non-core\" NE proteins9,10, including nuclear pore complexes (NPCs), fail to properly assemble. Consequently, micronuclei have impaired nuclear import, and key nuclear proteins required to maintain the integrity of the NE and the genome fail to accumulate normally. We show that densely bundled spindle microtubules inhibit non-core NE assembly, leading to an irreversible NE assembly defect. Accordingly, experimental manipulations that position missegregated chromosomes away from the spindle correct defective NE assembly, prevent spontaneous NE disruption, and suppress DNA damage in micronuclei. Our findings indicate that chromosome segregation and NE assembly are only loosely coordinated through the timing of mitotic spindle disassembly. The absence of precise regulatory controls can explain why errors during mitotic exit are frequent, and a major trigger for catastrophic genome rearrangements5,6.

cell biology↗

bioRxiv2017

Three-Dimensional Binocular Eye-Hand Coordination in Normal Vision and with Simulated Visual Impairment

Sensorimotor coupling in healthy humans is demonstrated by the higher accuracy of visually tracking intrinsically-rather than extrinsically-generated hand movements in the fronto-parallel plane. It is unknown whether this coupling also facilitates vergence eye movements for tracking objects in depth, or can overcome symmetric or asymmetric binocular visual impairments. Human observers were therefore asked to track with their gaze a target moving horizontally or in depth. The movement of the target was either directly controlled by the observer's hand or followed hand movements executed by the observer in a previous trial. Visual impairments were simulated by blurring stimuli independently in each eye. Accuracy was higher for self-generated movements in all conditions, demonstrating that motor signals are employed by the oculomotor system to improve the accuracy of vergence as well as horizontal eye movements. Asymmetric monocular blur affected horizontal tracking less than symmetric binocular blur, but impaired tracking in depth as much as binocular blur. There was a critical blur level up to which pursuit and vergence eye movements maintained tracking accuracy independent of blur level. Hand-eye coordination may therefore help compensate for functional deficits associated with eye disease and may be employed to augment visual impairment rehabilitation.

neuroscience↗

bioRxiv2017

Aging and neurodegeneration are associated with increased mutations in single human neurons

It has long been hypothesized that aging and neurodegeneration are associated with somatic mutation in neurons; however, methodological hurdles have prevented testing this hypothesis directly. We used single-cell whole-genome sequencing to perform genome-wide somatic single-nucleotide variant (sSNV) identification on DNA from 161 single neurons from the prefrontal cortex and hippocampus of fifteen normal individuals (aged 4 months to 82 years) as well as nine individuals affected by early-onset neurodegeneration due to genetic disorders of DNA repair (Cockayne syndrome and Xeroderma pigmentosum). sSNVs increased approximately linearly with age in both areas (with a higher rate in hippocampus) and were more abundant in neurodegenerative disease. The accumulation of somatic mutations with age--which we term genosenium--shows age-related, region-related, and disease-related molecular signatures, and may be important in other human age-associated conditions.\n\nOne-Sentence SummarySomatic single-nucleotide variants accumulate in human neurons in aging with regional specificity and in progeroid diseases.

genomics↗

bioRxiv2017

Linked-read analysis identifies mutations in single-cell DNA sequencing data

Whole-genome sequencing of DNA from single cells has the potential to reshape our understanding of the mutational heterogeneity in normal and disease tissues. A major difficulty, however, is distinguishing artifactual mutations that arise from DNA isolation and amplification from true mutations. Here, we describe linked-read analysis (LiRA), a method that utilizes phasing of somatic single nucleotide variants with nearby germline variants to identify true mutations, thereby allowing accurate estimation of somatic mutation rates at the single cell level.

bioinformatics↗