CDC-48/p97 Coordinates CDT-1 Degradation with GINS Chromatin Dissociation to Ensure Faithful DNA Replication
| Autor: | Olaf Stemmann, Thorsten Hoppe, Remi Sonneville, Anton Gartner, M. Orth, Paul A. Pirson, J. Julian Blow, André Franz |
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| Rok vydání: | 2011 |
| Předmět: |
Genetics
biology Eukaryotic DNA replication Cell Biology Pre-replication complex GINS Cell biology DNA replication factor CDT1 Licensing factor Control of chromosome duplication Minichromosome maintenance biology.protein Origin recognition complex Molecular Biology health care economics and organizations |
| Zdroj: | Molecular Cell. 44(1):85-96 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2011.08.028 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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