Humanizing the yeast origin recognition complex

Clare S. K. Lee, Ming Fung Cheung, Jinsen Li, Yongqian Zhao, Wai Hei Lam, Vincy Ho, Remo Rohs, Yuanliang Zhai (), Danny Leung () and Bik-Kwoon Tye ()
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Clare S. K. Lee: The University of Hong Kong
Ming Fung Cheung: The Hong Kong University of Science & Technology
Jinsen Li: University of Southern California
Yongqian Zhao: The Hong Kong University of Science & Technology
Wai Hei Lam: The University of Hong Kong
Vincy Ho: The Hong Kong University of Science & Technology
Remo Rohs: University of Southern California
Yuanliang Zhai: The University of Hong Kong
Danny Leung: The Hong Kong University of Science & Technology
Bik-Kwoon Tye: The Hong Kong University of Science & Technology

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-020-20277-y

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