- DNA Repair Mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- Microtubule and mitosis dynamics
- Ubiquitin and proteasome pathways
- Mitochondrial Function and Pathology
- Cardiomyopathy and Myosin Studies
- African history and culture studies
- Biochemical and Molecular Research
- Cancer, Hypoxia, and Metabolism
- South African History and Culture
- Growth Hormone and Insulin-like Growth Factors
- Genomics and Chromatin Dynamics
- Eicosanoids and Hypertension Pharmacology
- Enzyme Structure and Function
- Legal Issues in South Africa
- Photosynthetic Processes and Mechanisms
- Mosquito-borne diseases and control
- Protein Degradation and Inhibitors
- Protein Kinase Regulation and GTPase Signaling
- Autophagy in Disease and Therapy
- Cardiac Valve Diseases and Treatments
- Receptor Mechanisms and Signaling
- Atrial Fibrillation Management and Outcomes
- Race, History, and American Society
- Architecture, Design, and Social History
Molecular Oncology (United States)
2021
University of California, San Diego
2014-2020
Ludwig Cancer Research
2014-2019
Ludwig Cancer Research
2015
The AAA+ family ATPase TRIP13 is a key regulator of meiotic recombination and the spindle assembly checkpoint, acting on signaling proteins conserved HORMA domain family. Here we present structure Caenorhabditis elegans ortholog PCH-2, revealing new protein remodelers. PCH-2 possesses substrate-recognition related to those remodelers NSF p97, while its overall hexameric architecture likely structural mechanism bear close similarities bacterial unfoldase ClpX. We find that TRIP13, aided by...
The meiotic chromosome axis plays key roles in organization and recombination, yet the underlying protein components of this structure are highly diverged. Here, we show that 'axis core proteins' from budding yeast (Red1), mammals (SYCP2/SYCP3), plants (ASY3/ASY4) evolutionarily related play equivalent assembly. We first identify 'closure motifs' each complex recruit HORMADs, master regulators recombination. next find proteins form homotetrameric (Red1) or heterotetrameric (SYCP2:SYCP3...
The outbreak of the Zika virus (ZIKV) has been associated with increased incidence congenital malformations. Although recent efforts have focused on vaccine development, treatments for infected individuals are needed urgently. Sofosbuvir (SOF), an FDA-approved nucleotide analog inhibitor Hepatitis C (HCV) RNA-dependent RNA polymerase (RdRp) was recently shown to be protective against ZIKV both in vitro and vivo. Here, we show that SOF protected human neural progenitor cells (NPC) 3D...
The ubiquitin conjugating enzyme UBE2W catalyzes non-canonical ubiquitination on the N-termini of proteins, although its substrate repertoire remains unclear. To identify endogenous N-terminally-ubiquitinated substrates, we discover four monoclonal antibodies that selectively recognize tryptic peptides with an N-terminal diglycine remnant, corresponding to sites ubiquitination. Importantly, these do not isopeptide-linked (ubiquitin) modifications lysine. We solve structure one such antibody...
In the two cell divisions of meiosis, diploid genomes are reduced into complementary haploid sets through discrete, two-step removal chromosome cohesion, a task carried out in most eukaryotes by protecting cohesion at centromere until second division. without defined centromeres, however, alternative strategies have been innovated. The best-understood these is found nematode Caenorhabditis elegans : after single off-center crossover divides segments, or arms, several chromosome-associated...
In response to the threat posed by Union of South Africa, citizens and politicians in Lesotho have constructed a na-tional identity using symbols Moshoeshoe such as monu-ments holidays. One monument is Moshoeshoe's mountain fortress Thaba-Bosiu. Its use site for political events its prominent place popular legends illustrate transformation Thaba-Bosiu into honor Moshoeshoe. The emergence Thota-ea-Moli symbol illustrates contribution "invented" traditions consciousness. development national...
Abstract In the two cell divisions of meiosis, diploid genomes are reduced into complementary haploid sets through discrete, two-step removal chromosome cohesion, a task carried out in most eukaryotes by protecting cohesion at centromere until second division. without defined centromeres, however, alternative strategies have been innovated. The best-understood these is that used nematode Caenorhabditis elegans , where upon division segments or arms single off-center crossover, several...
Abstract The meiotic chromosome axis plays key roles in organization and recombination, yet the underlying protein components of this structure are highly diverged. Here, we show that “axis core proteins” from budding yeast (Red1), mammals (SYCP2/SYCP3), plants (ASY3/ASY4) evolutionarily related play equivalent assembly. We first identify motifs each complex recruit HORMADs, master regulators recombination. next find complexes form homotetrameric (Red1) or heterotetrameric (SYCP2:SYCP3...