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 ORCID: https://orcid.org/0000-0002-9524-5849, 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:	18 Jun 2026 20:13
URI:	https://ueaeprints.uea.ac.uk/id/eprint/95445
DOI:	10.1016/j.molcel.2011.08.028

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