Researchers from the Hong Kong University of Science and Technology (HKSUST) and the University of Hong Kong (HKU) recently demonstrated that the selectivity determinant of Origin Recognition Complex (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 (genomic nucleosome profile), a characteristic feature shared by human ORC.