Publication: A CDK-regulated chromatin segregase promoting chromosome replication.
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Date
2021-09-01
Authors
Chacin, Erika
Bansal, Priyanka
Reusswig, Karl-Uwe
Diaz-Santin, Luis M
Ortega, Pedro
Vizjak, Petra
Gómez-González, Belen
Müller-Planitz, Felix
Aguilera, Andrés
Pfander, Boris
Advisors
Journal Title
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Volume Title
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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 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.
Description
MeSH Terms
Adenosine Triphosphatases
Cell Cycle Checkpoints
Chromatin
Chromatin Assembly and Disassembly
Chromosomal Proteins, Non-Histone
Cyclin-Dependent Kinases
DNA
DNA Replication
Histones
Humans
Phosphorylation
S Phase
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
Transcription Factors
Cell Cycle Checkpoints
Chromatin
Chromatin Assembly and Disassembly
Chromosomal Proteins, Non-Histone
Cyclin-Dependent Kinases
DNA
DNA Replication
Histones
Humans
Phosphorylation
S Phase
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
Transcription Factors