CDC-48/p97 coordinates CDT-1 degradation with GINS chromatin dissociation to ensure faithful DNA replication

Franz, André, Orth, Michael, Pirson, Paul A., Sonneville, Remi, Blow, J. Julian, Gartner, Anton, Stemmann, Olaf and Hoppe, Thorsten (2011) CDC-48/p97 coordinates CDT-1 degradation with GINS chromatin dissociation to ensure faithful DNA replication. Molecular Cell, 44 (1). pp. 85-96. ISSN 1097-2765

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Abstract

Faithful transmission of genomic information requires tight spatiotemporal regulation of DNA replication factors. In the licensing step of DNA replication, CDT-1 is loaded onto chromatin to subsequently promote the recruitment of additional replication factors, including CDC-45 and GINS. During the elongation step, the CDC-45/GINS complex moves with the replication fork; however, it is largely unknown how its chromatin association is regulated. Here, we show that the chaperone-like ATPase CDC-48/p97 coordinates degradation of CDT-1 with release of the CDC-45/GINS complex. C. elegans embryos lacking CDC-48 or its cofactors UFD-1/NPL-4 accumulate CDT-1 on mitotic chromatin, indicating a critical role of CDC-48 in CDT-1 turnover. Strikingly, CDC-48(UFD-1/NPL-4)-deficient embryos show persistent chromatin association of CDC-45/GINS, which is a consequence of CDT-1 stabilization. Moreover, our data confirmed a similar regulation in Xenopus egg extracts, emphasizing a conserved coordination of licensing and elongation events during eukaryotic DNA replication by CDC-48/p97.

Item Type: Article
Faculty \ School:
Depositing User: LivePure Connector
Date Deposited: 10 Jun 2024 10:32
Last Modified: 10 Jun 2024 10:32
URI: https://ueaeprints.uea.ac.uk/id/eprint/95445
DOI: 10.1016/j.molcel.2011.08.028

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