You can help! If you notice any inaccuracies, please sign in and mark papers as correct or incorrect matches. If you identify any major omissions or other inaccuracies in the publication list, please let us know. Beth Sullivan - Publications Affiliations:.
Correction: Going the distance: Neocentromeres make long-range contacts with heterochromatin. The Journal of Cell Biology. Going the distance: Neocentromeres make long-range contacts with heterochromatin. Alpha satellite DNA biology: finding function in the recesses of the genome. Centromere Silencing Mechanisms.
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Progress in Molecular and Subcellular Biology. Developmental Cell. Human centromere repositioning within euchromatin after partial chromosome deletion. Genomic variation within alpha satellite DNA influences centromere location on human chromosomes with metastable epialleles. Genome Research. Inheritance of the CENP-A chromatin domain is spatially and temporally constrained at human centromeres.
A Molecular View of Kinetochore Assembly and Function
The past, present, and future of human centromere genomics. Nucleolar organization, ribosomal DNA array stability, and acrocentric chromosome integrity are linked to telomere function. Plos One.
Neocentromeres: a place for everything and everything in its place. Trends in Genetics : Tig. Sullivan BA , et al. Functional epialleles at an endogenous human centromere.
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Foreword: the centromere and kinetochore in creatures great and small. Dicentric chromosomes: unique models to study centromere function and inactivation. The file will be sent to your Kindle account. It may takes up to minutes before you received it. Please note you've to add our email mailer bookmail.
Read more. Post a Review. You can write a book review and share your experiences. Other readers will always be interested in your opinion of the books you've read. At the molecular level, we study yeast protein activity biochemically in yeast cell extracts or in in vitro assays using recombinant proteins produced in bacteria, yeast or insect cells.
Assays include co-IPs, in vitro protein-centromere binding studies using gel retardation analysis, in vitro protein reconstitution and affinity measurements using ITC or chromatography, kinase assays followed by mass spectroscopic identification of phosphorylated residues.
Structural protein studies are performed by hydrodynamics gel filtration plus glycerol gradient density velocity ultracentrifugation and crystallographic analysis of recombinant proteins following crystallization at our in-house crystallography facility. By integrating a variety of methodologies we wish to obtain a most detailed understanding of the proteins and regulators that drive chromosome segregation in yeast, and ultimately, in human cells.
Research projects 1 Activity and regulation of Cnn1 at yeast kinetochores Cnn1 is a conserved kinetochore protein CENP-T in humans that localizes to centromeric chromatin via its C-terminal histone fold domain Figure 2.
Its N-terminal tail extends inside the kinetochore and binds to the globular heads of the SpcSpc25 dimer of the Ndc80 complex further comprises Ndc80 and Nuf2. The binding of Cnn1 to SpcSpc25 is regulated by phosphorylation Cdc28 and Mps1 kinases and stabilizes the Ndc80 complex at the kinetochore.
However, to bind to the Ndc80 complex, the tail of Cnn1 must compete with the tail of Dsn1, a subunit of the tetrameric Mtw1 complex Mis12 complex in humans. From G1 to metaphase, the high copy number of the Mtw1 complex and phospho-inhibition of the Cnn1 tail favors Mtw1-Ndc80 complex binding, creating a rigid kinetochore structure. At the metaphase-anaphase transition, Cnn1 levels at kinetochores increase equaling those of the Mtw1 and Ndc80 complexes.
The Kinetochore:: From Molecular Discoveries to Cancer Therapy
In addition, the degradation of Mps1, decrease in Cdc28 activity due to cyclin degradation, and an increased dephosphorylation of Cnn1 allow the latter to bind to the Ndc80 complex, resulting in a looser kinetochore structure. The latter may promote the binding of the Ndc80 complex to microtubules and to the microtubule-surrounding Dam1 ring complex, thereby supporting the transduction of forces generated by microtubule depolymerization that are required to mediate chromosome segregation.
We study at the molecular level how Cnn1 activity and levels at kinetochores are controlled during the cell cycle. We found that its nucleolar localization is dynamic and cell cycle stage dependent. Indeed, using a rio1 mutant we showed that yeast lacking nuclear Rio1 activity is unable to segregate the rDNA locus and finalize genome transmission at exit from mitosis.
Our study of how Rio1 orchestrates chromosome segregation in time and space we will generate new insights into a most basic mitotic process and suggest how an anomalous expression of Rio1, as observed in various tumors, may underlie aneuploidy in dividing cells. All publications from Cerca nel sito. Un istituto di riferimento dove la ricerca sui tumori diventa cura in tempo reale. Activities During mitosis, kinetochores orchestrate chromosome transmission from the mother into the daughter cells.