A5010374555- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- DNA Repair Mechanisms
- DNA and Nucleic Acid Chemistry
- RNA and protein synthesis mechanisms
- Nuclear Structure and Function
- Dysphagia Assessment and Management
- RNA Research and Splicing
- Tracheal and airway disorders
- Cervical and Thoracic Myelopathy
- Sexual Differentiation and Disorders
- Plant nutrient uptake and metabolism
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Photosynthetic Processes and Mechanisms
- Telomeres, Telomerase, and Senescence
- Chromosomal and Genetic Variations
University of North Carolina at Chapel Hill
2017-2024
Henry Ford Hospital
2016
Chromatin exhibits increased mobility on DNA damage, but the biophysical basis for this behavior remains unknown. To explore mechanisms that drive damage-induced chromosome mobility, we use single-particle tracking of tagged chromosomal loci during interphase in live yeast cells together with polymer models chromatin chains. Telomeres become mobilized from sites nuclear envelope and pericentromere expands after exposure to DNA-damaging agents. The magnitude induced by a single double-strand...
Regions of highly repetitive DNA, such as those found in the nucleolus, show a self-organization that is marked by spatial segregation and frequent self-interaction. The mechanisms underlie sequestration these sub-domains are largely unknown. Using stochastic, bead-spring representation chromatin budding yeast, we find enrichment protein-mediated, dynamic chromosomal cross-links recapitulates segregation, morphology self-interaction nucleolus. Rates crosslinking have profound consequences on...
Abstract The revolution in understanding higher order chromosome dynamics and organization derives from treating the as a chain polymer adapting appropriate polymer-based physical principles. Using basic principles, such entropic fluctuations timescales of relaxation Rouse chains, one can recapitulate dominant features chromatin motion observed vivo. An emerging challenge is to relate mechanical properties more nuanced organizational principles ubiquitous DNA loops. Toward this goal, we...
Chromosomes with two centromeres provide a unique opportunity to study chromosome breakage and DNA repair using completely endogenous cellular machinery. Using conditional transcriptional promoter control the second centromere, we are able activate dicentric follow appearance of products. We find that rate products resulting from homology-based mechanisms exceeds expected based on their limited centromere homology (340 bp) distance one another (up 46.3 kb). In order identify whether breaks...
DNA double-strand breaks arise in vivo when a dicentric chromosome (two centromeres on one chromosome) goes through mitosis with the two attached to opposite spindle pole bodies. Repair of DSBs generates phenotypic diversity due range monocentric derivative chromosomes that arise. To explore whether may be differentially repaired as function their spatial position chromosome, we have examined structure from cells containing suite which distance between ranges 6.5 kb 57.7 kb. Two major...
Significance There is an epigenetic requirement for de novo kinetochore assembly in budding yeast. Perturbations that delay S phase suppress defects. We propose a role replication fork progression allowing DNA to adopt configurations conducive centromere function. The function of stalling upon encounters with damage or other blockades allow time thermal fluctuations the chain explore numerous configurations. Biasing thermodynamics provides mechanism facilitate macromolecular assembly,...
XMAP215/Dis1 family proteins are potent microtubule polymerases, critical for mitotic spindle structure and dynamics. While polymerase activity is driven by an N-terminal tumor overexpressed gene (TOG) domain array, proper cellular localization a requisite full mediated C-terminal domain. Structural insight into the domain's architecture mechanism remain outstanding. We present crystal of
A key feature of chromosome segregation is the ability to sense tension between sister kinetochores. DNA kinetochores must be packaged in a way that sustains propagation from one kinetochore its sister, approximately 1 micron away. molecular bottlebrush consisting primary axis populated with crowded array side chains provides means build over length scales considerably larger than stiffness individual elements, is, polymer. Evidence for organization chromatin comes genetic, cell biological,...