Please use this identifier to cite or link to this item: https://hdl.handle.net/1783.1/109169
Humanizing the yeast origin recognition complex
| Author |
Lee, Clara S.K.
Cheung, Ming Fung Li, Jinsen Zhao, Yongqian Lam, Wai Hei Ho, Vincy Wing Sze Rohs, Remo Zhai, Yuanliang 
Leung, Danny
Tye, Bik Kwoon |
|---|---|
| Issue Date | 2021 |
| Source | Nature Communications, v. 12, (1), January 2021, article number 33 |
| Abstract | The Origin Recognition Complex (ORC) is an evolutionarily conserved six-subunit protein complex that binds specific sites at many locations to coordinately replicate the entire eukaryote genome. Though highly conserved in structure, ORC’s selectivity for replication origins has diverged tremendously between yeasts and humans to adapt to vastly different life cycles. In this work, we demonstrate that the selectivity determinant of ORC for DNA binding lies in a 19-amino acid insertion helix in the Orc4 subunit, which is present in yeast but absent in human. Removal of this motif from Orc4 transforms the yeast ORC, which selects origins based on base-specific binding at defined locations, into one whose selectivity is dictated by chromatin landscape and afforded with plasticity, as reported for human. Notably, the altered yeast ORC has acquired an affinity for regions near transcriptional start sites (TSSs), which the human ORC also favors. © 2021, The Author(s). |
| DOI | 10.1038/s41467-020-20277-y |
| ISSN | 2041-1723 |
| Language | English |
| Type | Article |
| Access |
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