title: Ring of Change: CDC48/p97 Drives Protein Dynamics at Chromatin.
abstract: The dynamic composition of proteins associated with nuclear DNA is a fundamental property of chromosome biology. In the chromatin compartment dedicated protein complexes govern the accurate synthesis and repair of the genomic information and define the state of DNA compaction in vital cellular processes such as chromosome segregation or transcription. Unscheduled or faulty association of protein complexes with DNA has detrimental consequences on genome integrity. Consequently, the association of protein complexes with DNA is remarkably dynamic and can respond rapidly to cellular signaling events, which requires tight spatiotemporal control. In this context, the ring-like AAA+ ATPase CDC48/p97 emerges as a key regulator of protein complexes that are marked with ubiquitin or SUMO. Mechanistically, CDC48/p97 functions as a segregase facilitating the extraction of substrate proteins from the chromatin. As such, CDC48/p97 drives molecular reactions either by directed disassembly or rearrangement of chromatin-bound protein complexes. The importance of this mechanism is reflected by human pathologies linked to p97 mutations, including neurodegenerative disorders, oncogenesis, and premature aging. This review focuses on the recent insights into molecular mechanisms that determine CDC48/p97 function in the chromatin environment, which is particularly relevant for cancer and aging research.
authors.affiliation: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, Institute for Genetics, University of Cologne Cologne, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Franz
authors.affiliation: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, Institute for Genetics, University of Cologne Cologne, Germany.
authors.forename: Leena
authors.initials: L
authors.lastname: Ackermann
authors.affiliation: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, Institute for Genetics, University of Cologne Cologne, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Hoppe
keywords: CDC48; DNA repair; SUMO; chromatin; p97; replication; ubiquitin