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Ben L. Carty
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Journal Articles
Journal:
Journal of Cell Biology
Journal of Cell Biology (2021) 220 (3): e202101027.
Published: 10 February 2021
Abstract
Murillo-Pineda and colleagues (2021. J. Cell Biol. https://doi.org/10.1083/jcb.202007210 ) use CRISPR-Cas9–based genetic engineering in human cells to induce a new functional centromere at a naive chromosomal site. Long-read DNA sequencing at the neocentromere provides firm evidence that centromere establishment is a truly epigenetic event.
Journal Articles
In Special Collection:
Stem Cell Collection 2020
Anna Ada Dattoli, Ben L. Carty, Antje M. Kochendoerfer, Conall Morgan, Annie E. Walshe, Elaine M. Dunleavy
Journal:
Journal of Cell Biology
Journal of Cell Biology (2020) 219 (4): e201910084.
Published: 12 March 2020
Abstract
Centromeres are epigenetically defined by CENP-A–containing chromatin and are essential for cell division. Previous studies suggest asymmetric inheritance of centromeric proteins upon stem cell division; however, the mechanism and implications of selective chromosome segregation remain unexplored. We show that Drosophila female germline stem cells (GSCs) and neuroblasts assemble centromeres after replication and before segregation. Specifically, CENP-A deposition is promoted by CYCLIN A, while excessive CENP-A deposition is prevented by CYCLIN B, through the HASPIN kinase. Furthermore, chromosomes inherited by GSCs incorporate more CENP-A, making stronger kinetochores that capture more spindle microtubules and bias segregation. Importantly, symmetric incorporation of CENP-A on sister chromatids via HASPIN knockdown or overexpression of CENP-A, either alone or together with its assembly factor CAL1, drives stem cell self-renewal. Finally, continued CENP-A assembly in differentiated cells is nonessential for egg development. Our work shows that centromere assembly epigenetically drives GSC maintenance and occurs before oocyte meiosis.