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XB-ART-3672
J Cell Biol 2004 Apr 26;1652:181-90. doi: 10.1083/jcb.200311044.
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The role of Cdc6 in ensuring complete genome licensing and S phase checkpoint activation.

Oehlmann M , Score AJ , Blow JJ .


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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.

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Species referenced: Xenopus laevis
Genes referenced: cdc45 cdc6 cdt1 chek1 gmnn mcm2 mcm4 mcm5 mcm6.2 mcm7 orc1 orc2 pcna rpa1


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References [+] :
Alexandrow, Cdc6 chromatin affinity is unaffected by serine-54 phosphorylation, S-phase progression, and overexpression of cyclin A. 2004, Pubmed