A CDK-regulated chromatin segregase promoting chromosome replication
Díaz Santín, Luis M.
Ortega Moreno, Pedro
Gómez González, Belén
Aguilera López, Andrés
Cheung, Alan C. M.
Kurat, Christoph F.
|Department||Universidad de Sevilla. Departamento de Genética|
|Abstract||The replication of chromosomes during S phase is critical for cellular and organismal function. Replicative stress can result in genome instability, which is a major driver of cancer. Yet how chromatin is made accessible ...
The replication of chromosomes during S phase is critical for cellular and organismal function. Replicative stress can result in genome instability, which is a major driver of cancer. Yet how chromatin is made accessible during eukaryotic DNA synthesis is poorly understood. Here, we report the characterization of a chromatin remodeling enzyme—Yta7—entirely distinct from classical SNF2-ATPase family remodelers. Yta7 is a AAA+ -ATPase that assembles into ~1 MDa hexameric complexes capable of segregating histones from DNA. The Yta7 chromatin segregase promotes chromosome replication both in vivo and in vitro. Biochemical reconstitution experiments using purified proteins revealed that the enzymatic activity of Yta7 is regulated by S phase-forms of Cyclin-Dependent Kinase (S-CDK). S-CDK phosphorylation stimulates ATP hydrolysis by Yta7, promoting nucleosome disassembly and chromatin replication. Our results present a mechanism for how cells orchestrate chromatin dynamics in co-ordination with the cell cycle machinery to promote genome duplication during S phase.
|Project ID.||ID 213249687
|Citation||Chacin, E., Bansal, P., Reusswig, K., Díaz Santín, L.M., Ortega Moreno, P., Vizjak, P.,...,Kurat, C.F. (2021). A CDK-regulated chromatin segregase promoting chromosome replication. Nature Communications, 12 (1), 5224.|