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Oehlmann, Maren, Score, Alan J. and Blow, J. Julian 
ORCID: https://orcid.org/0000-0002-9524-5849
(2004)
The role of Cdc6 in ensuring complete genome licensing and S phase checkpoint activation.
Journal of Cell Biology, 165 (2).
pp. 181-190.
ISSN 0021-9525
Abstract
Before S phase, cells license replication origins for initiation by loading them with Mcm2-7 heterohexamers. This process is dependent on Cdc6, which is recruited to unlicensed origins. Using Xenopus egg extracts we show that although each origin can load many Mcm2-7 hexamers, the affinity of Cdc6 for each origins drops once it has been licensed by loading the first hexamers. This encourages the distribution of at least one Mcm2-7 hexamer to each origin, and thereby helps to ensure that all origins are licensed. Although Cdc6 is not essential for DNA replication once licensing is complete, Cdc6 regains a high affinity for origins once replication forks are initiated and Mcm2-7 has been displaced from the origin DNA. We show that the presence of Cdc6 during S phase is essential for the checkpoint kinase Chk1 to become activated in response to replication inhibition. These results show that Cdc6 plays multiple roles in ensuring precise chromosome duplication.
| Item Type: | Article |
|---|---|
| Faculty \ School: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 10 Jun 2024 16:30 |
| Last Modified: | 25 Sep 2024 17:52 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/95517 |
| DOI: | 10.1083/jcb.200311044 |
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