Abstract

The Origin Recognition Complex (ORC) is a six-subunit complex that is highly conserved from yeasts to humans. However, the mechanism for finding its binding sites diverged from a base-specific mechanism in yeasts to a site-specific but base-agnostic mechanism in humans. Based on the atomic model of the yeast ORC bound to replication origin DNA, the 19-aa base-specificity determinant that interacts with the invariant Ts in the consensus sequence of the yeast origin DNA is missing in metazoans. We studied the physiological effect of removing this crucial element of ORC in yeast and found that the altered ORC∗ behaved more like a human ORC.

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