A5045636210- Genetic Neurodegenerative Diseases
- DNA Repair Mechanisms
- Mitochondrial Function and Pathology
- Microtubule and mitosis dynamics
- Chromosomal and Genetic Variations
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Fungal and yeast genetics research
- Cardiomyopathy and Myosin Studies
Tufts University
2020-2024
Max Perutz Labs
2020-2022
University of Vienna
2020-2022
Abstract CANVAS is a recently characterized repeat expansion disease, most commonly caused by homozygous expansions of an intronic (A2G3)n in the RFC1 gene. There are multitude motifs found human population at this locus, some which pathogenic and others benign. In study, we conducted structure-functional analyses nonpathogenic (A4G)n repeats. We that pathogenic, but not nonpathogenic, presents potent, orientation-dependent impediment to DNA polymerization vitro. The pattern blockage...
Abstract H-DNA is an intramolecular DNA triplex formed by homopurine-homopyrimidine mirror repeats. Since its discovery, the field has advanced from characterizing structure in vitro to discovering existence and role vivo. interacts with cellular machinery unique ways, stalling RNA polymerases causing genome. The foundational S1 nuclease chemical probing technologies originally used show formation have been updated combined genome-wide sequencing methods for large-scale mapping of secondary...
The inner kinetochore and microtubule binding activities of the Chromosomal Passenger Complex are sufficient to promote accurate chromosome segregation. In addition, two distinct pathways target CPC different attachment states, as an centromere-targeting pathway is primarily responsible for complex enrichment at unattached kinetochores
Abstract Large-scale expansion of (GAA)n repeats in the first intron FXN gene is responsible for severe neurodegenerative disease, Friedreich’s ataxia humans. We have previously conducted an unbiased genetic screen GAA repeat instability a yeast experimental system. The majority genes that came from this encoded components DNA replication machinery, strongly implying irregularities are at heart expansions. This screen, however, also produced two unexpected hits: members CST complex, CDC13...
Trinucleotide repeats, including Friedreich's ataxia (GAA)n become pathogenic upon expansions during DNA replication and repair. Here, we show that deficiency of the essential replisome component Mcm10 dramatically elevates repeat instability in a budding yeast model by loss proper CMG helicase interaction. Supporting this conclusion, live-cell microscopy experiments reveal increased fork stalling at mcm10-1 cells. Unexpectedly, viability strains containing single (GAA)100 an chromosomal...
Abstract Chromosome biorientation is established by the four-member chromosomal passenger complex (CPC) through phosphorylation of incorrect kinetochore-microtubule attachments. During chromosome alignment, CPC localizes to inner centromere, kinetochore and spindle microtubules. Here we show that a small region subunit INCENP/Sli15 required target all three these locations in budding yeast. This region, SAH, essential for outer substrates, segregation, viability. By restoring each...