Crm1 locks up replication factors

Limiting replication to a single round per division is critical for cells, but the proteins that control the process in metazoans have remained obscure. Now, Ryuji Yamaguchi and John Newport (University of California, San Diego, CA) find that Crm1 sequesters MCM helicase in the nucleus, preventing it from binding to the chromatin where it would initiate a new round of DNA synthesis.

Working in Xenopus egg extracts, the team found that, although the prevention of rereplication is dependent on high concentrations of Ran-GTP and Cdk2 kinase activity, it does not require nuclear export of MCM. That means that Crm1 may have a new mechanism of action, since all of its previously known functions involved nuclear transport.

“We think this makes sense,” says Newport, “because it is an extremely rapid mechanism for inactivating MCM.” If the repression required transporting MCM...