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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
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: | 25 Sep 2024 17:51 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/95445 |
| DOI: | 10.1016/j.molcel.2011.08.028 |
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