A5065909906- Microtubule and mitosis dynamics
- Genomics and Chromatin Dynamics
- Ubiquitin and proteasome pathways
- DNA Repair Mechanisms
- Chromosomal and Genetic Variations
- Biomedical and Engineering Education
- RNA Research and Splicing
- Career Development and Diversity
- Genomic variations and chromosomal abnormalities
- Cancer-related Molecular Pathways
- Fungal and yeast genetics research
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Plant nutrient uptake and metabolism
- Cancer therapeutics and mechanisms
- Microfluidic and Bio-sensing Technologies
- Single-cell and spatial transcriptomics
- Mitochondrial Function and Pathology
- Photosynthetic Processes and Mechanisms
- Cellular transport and secretion
- DNA and Nucleic Acid Chemistry
- Academic integrity and plagiarism
- Genetics, Bioinformatics, and Biomedical Research
- Health and Medical Research Impacts
- Autophagy in Disease and Therapy
Gonzaga University
2020-2024
The University of Texas at El Paso
2015-2022
Division of Undergraduate Education
2022
The University of Texas Southwestern Medical Center
2007-2015
University of Minnesota
2003-2015
University of Minnesota System
2015
Minneapolis Institute of Arts
2015
Howard Hughes Medical Institute
2008-2014
University of Minnesota Medical Center
2006-2010
Southwestern Medical Center
2008-2010
Most cancer cells are characterized by aneuploidy, an abnormal number of chromosomes. We have identified a clue to the mechanistic origins aneuploidy through integrative genomic analyses human tumors. A diverse range tumor types were found harbor deletions or inactivating mutations STAG2, gene encoding subunit cohesin complex, which regulates separation sister chromatids during cell division. Because STAG2 is on X chromosome, its inactivation requires only single mutational event. Studying...
The precision of the metaphase-anaphase transition ensures stable genetic inheritance. spindle checkpoint blocks anaphase onset until last chromosome biorients at metaphase plate, then bonds between sister chromatids are removed and disjoined segregate to poles. But, how separation is triggered not fully understood.We identify PIASgamma as a human E3 sumo ligase required for timely efficient chromatid separation. In cells lacking PIASgamma, normal plates form, but activated, leading...
Abstract Background Proteins containing ubiquitin-like (UBL) and ubiquitin associated (UBA) domains have been suggested to shuttle ubiquitinated substrates the proteasome for degradation. There are three UBL-UBA proteins in budding yeast: Ddi1, Dsk2 Rad23, which demonstrated play regulatory roles targeting An involvement of these cell cycle related events has also reported. We tested whether act redundantly cycle. Results Here we show that partially redundant roles. RAD23 is with DDI1 DSK2 ,...
Genome stability is ensured by multiple surveillance mechanisms that monitor the duplication, segregation, and integrity of genome throughout cell cycle. Depletion components spliceosome, a macromolecular machine essential for mRNA maturation gene expression, has been associated with increased DNA damage cycle defects. However, specific role spliceosome in these processes remained elusive, as different defects have reported depending on subunit depleted. Through detailed analysis after...
AbstractCheckpoint controls confer order to the cell cycle and help prevent genome instability. Here we discuss Topoisomerase II (Decatenation) Checkpoint which functions regulate mitotic progression so that chromosomes can be efficiently condensed in prophase segregated with high fidelity anaphase.
Topoisomerase II (Topo II) performs topological modifications on double-stranded DNA molecules that are essential for chromosome condensation, resolution, and segregation. In mammals, G2 metaphase cell cycle delays induced by Topo poisons have been proposed to be the result of checkpoint activation in response catenation state DNA. However, apparent lack such controls model organisms has excluded genetic proof checkpoints exist separable from conventional damage controls. But here, we define...
Abstract Key to faithful genetic inheritance is the cohesion between sister centromeres that physically links replicated chromatids and then abruptly lost at onset of anaphase. Misregulated causes aneuploidy, birth defects perhaps initiates cancers. Loss centromere controlled by spindle checkpoint thought depend on a ubiquitin ligase, Anaphase Promoting Complex/Cyclosome (APC). But here we present evidence APC pathway dispensable for separation anaphase in mammals, proceeds presence cyclin B...
AbstractClassically, chromosomal functions in DNA repair and sister chromatid association have been assigned to the cohesin proteins. More recent studies provided evidence that cohesins also localize centrosomes, which organize bipolar spindle during mitosis. Depletion of proteins is associated with multi-polar mitosis pole integrity compromised. However, defects after depletion could be an indirect consequence a cohesion defect might impact centrosome via alterations microtubule network....
Advancement of the scientific enterprise relies on individuals conducting research in an ethical and responsible manner. Educating emergent scholars principles ethics/responsible conduct (E/RCR) is therefore critical to ensuring such advancement. The recent impetus include authentic opportunities as part undergraduate curriculum, via course-based experiences (CUREs), has been shown increase cognitive noncognitive student outcomes. Because these important benefits, CUREs are becoming more...
AbstractMulti-polar mitosis is strongly linked with aggressive cancers and it a histological diagnostic of tumor-grade. However, factors that cause chromosomes to segregate more than two spindle poles are not well understood. Here we show cohesins Rad21, Smc1 Smc3 required for bipolar in human cells. After Rad21 depletion, align at the metaphase plate spindles assemble most cases, but anaphase separated chromatids multiple poles. Time-lapse microscopy revealed often become split...
Background Proper regulation of the cohesion at centromeres human chromosomes is essential for accurate genome transmission. Exactly how maintained and then dissolved in anaphase not understood. Principal Findings We have investigated role cohesin complex cells both by depleting subunits using RNA interference also expressing a non-cleavable version Rad21 protein. depletion results aberrant anaphase, during which sister chromatids separate segregate an asynchronous fashion. However,...
Course-based undergraduate research experiences (CUREs) have been identified as a promising vehicle to broaden novices' participation in authentic scientific opportunities. While recent studies the bioeducation literature focused on influence of CUREs cognitive and non-cognitive student outcomes (e.g., attitudes motivation, science process skills development), few investigations examined extent which contextual features inherent such affect students' academic professional growth. Central...
The yeast separase proteins Esp1 and Cut1 are required for loss of sister chromatid cohesion that occurs at the moment anaphase onset. Circumstantial evidence has linked human to centromere separation anaphase, but a direct test role this enzyme is functionally conserved with lacking. Here we describe effects depletion from cells using RNA interference. Surprisingly, HeLa lacking delayed or arrest G2/M phase transition. This not likely due activation known checkpoint control, may be result...
Regulated separation of sister chromatids is the key event mitosis. Sister remain cohered from moment DNA duplication until anaphase. Two known factors account for cohesion: catenations and cohesin complexes. Premature loss centromeric cohesion prevented by spindle checkpoint. Here we show that sororin, a protein implicated in promoting through effects on complexes, involved maintenance response to Sororin-depleted cells reach prometaphase with are able form metaphase plates. However,...
Course-based undergraduate research experiences (CUREs), which often engage students as early freshman year, have become increasingly common in biology curricula. While many studies highlighted the benefits of CUREs, little attention has been paid to responsible and ethical conduct (RECR) education such contexts. Given this observation, we adopted a mixed methods approach explore extent RECR is being implemented assessed biological sciences CUREs nationwide. Survey semistructured interview...
Cohesin proteins help maintain the physical associations between sister chromatids that arise in S-phase and are removed anaphase. Recent studies found cohesins also localize to centrosomes, organelles organize mitotic bipolar spindle. We find cohesin protein Rad21 localizes centrosomes a manner is dependent upon known regulators of chromatid cohesion as well centrosome function. These data suggest functions at coordinate chromosomal cohesin.
Cohesin is a multiprotein ring complex that regulates 3D genome organization, sister chromatid cohesion, gene expression, and DNA repair. known to be ubiquitinated, although the mechanism, regulation, effects of cohesin ubiquitination remain poorly defined. We previously used editing introduce dual epitope tag into endogenous allele each 11 components in human HCT116 cells. Here we report mass spectrometry analysis dual-affinity purifications identified USP13 deubiquitinase as novel...