A CDK-regulated chromatin segregase promoting chromosome replication

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 similar to 1MDa 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.

Automated summary

Yta7 is a chromatin remodeling enzyme that promotes chromosome replication during S phase, forming hexameric complexes capable of segregating histones from DNA. Its enzymatic activity is regulated by S phase-forms of Cyclin-Dependent Kinase (S-CDK), which stimulates ATP hydrolysis by Yta7 to promote nucleosome disassembly and chromatin replication. These findings present a mechanism for how cells coordinate chromatin dynamics with the cell cycle machinery to ensure genome duplication during S phase.