Mechanism of Mcm2-7 Loading Creating symmetry from asymmetry —
generating the symmetric Mcm2-7 double hexamer structure at an
asymmetric origin site. Conserved origin sequence motifs are
represented by yellow boxes below the DNA. The head-to-head
arrangement of Mcm2-7 in the double-hexamer provides a molecular
basis for the establishment of bi-directional DNA replication
forks at an origin. But how are two Mcm2-7 hexamers loaded
cooperatively, yet in opposite orientation by one set of loading
factors? Or in other words, how is the symmetry of the Mcm2-7
double hexamer generated from an intrinsically asymmetric
origin/pre- RC (Figure 5)? Origin sites in yeast are
characterized by asymmetrically arranged conserved sequence
motifs, and ORC neither exhibits any structural symmetry nor
does it appear to bind symmetrically to origin sites. Do
multiple ORC complexes perhaps cooperate to mediate Mcm2-7
loading? Or does Cdc6 function in concert with ORC to mediate
the loading of the opposite Mcm2-7 hexamer? Subunit in