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Humanizing the yeast origin recognition complex
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DOI：10.1038/s41467-020-20277-y.png)
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Abstract
En 中文
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. In most model yeast species the Origin Recognition Complex (ORC) binds defined and species-specific base sequences while in humans what determines the binding appears to be more complex. Here the authors reveal that the yeast's ORC complex binding specificity is dependent on a 19-amino acid insertion helix in the Orc4 subunit which is lost in human.
Keywords:
DNA-REPLICATION
QUALITY-CONTROL
GENOME-SCALE
INITIATION
CHROMATIN
REVEALS
PROTEINS
SITES
PREDICTION
FEATURES
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