ORC3 and central nervous system cancer: It is unclear whether both pathways are used in vivo: a Meier-Gorlin syndrome mutant that maps to the C-terminal α-helix of ORC6 that interacts with ORC3 and inhibits ORC6 interaction with ORC1–5 also inhibits MCM loading in D. melanogaster35; however, depletion of ORC6 from human U2OS cells was shown to have no effect on MCM loading levels in a single cell cycle36, and an ORC6 knockout in glioma cells was observed to support cell viability and proliferation37.