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| Content Provider | PubMed Central |
|---|---|
| Author | Frigola, Jordi Remus, Dirk Mehanna, Amina Diffley, John F. X. |
| Abstract | The regulated loading of the Mcm2-7 DNA helicase into pre-replicative complexes (pre-RCs) at multiple replication origins ensures precise once per cell cycle replication in eukaryotic cells. Origin Recognition Complex (ORC), Cdc6 and Cdt1 load Mcm2-7 into a double hexamer bound around duplex DNA in an ATP-dependent reaction, but the molecular mechanism of this origin ‘licensing’ is still poorly understood. Here we show that both Mcm2-7 hexamers are recruited to origins by an essential, conserved C-terminal domain of Mcm3 which interacts with and stimulates the ATPase activity of ORC•Cdc6. ATP hydrolysis can promote Mcm2-7 loading, but can also promote Mcm2-7 release if components are missing or if ORC has been inactivated by cyclin-dependent kinase phosphorylation. Our work provides new insights into how origins are licensed and reveals a novel ATPase-dependent mechanism contributing to precise once per cell cycle replication. |
| Related Links | http://dx.doi.org/10.1038/nature11920 |
| Ending Page | 343 |
| Page Count | 5 |
| Starting Page | 339 |
| File Format | |
| ISSN | 14764687 |
| e-ISSN | 14764687 |
| Journal | Nature |
| Issue Number | 7441 |
| Volume Number | 495 |
| Language | English |
| Publisher Date | 2013-03-21 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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