Figure 7.

Hypothetical paradigms of the regulatory mechanisms underlying the functional cooperation between FACT and MCM complexes. (A) Putative models for the distinct roles of the two identified FACT-MCM complexes. As shown in Figure 3, the two assemblies may be recruited to the origin region in a temporal fashion, with FACT-MCM2/3/4/5 preceding FACT-MCM2/4/6/7. Both complexes are enzymatically active, and they may exert their activities, in two possible modes (I & II), at distinct and/or sequential stages during the early phase of DNA replication initiation (see Discussion). (B) The FACT-MCM complex constitutes an important activity that facilitates chromatin DNA unwinding during DNA replication [29]. Functional attributes of the FACT-MCM complexes are coordinated with the cell cycle. The temporal mode of such regulation is depicted in this diagram, in which the relative levels of the indicated functional attributes are represented. Origin association of the two FACT-MCM complexes reflects their distinct roles during origin establishment and replication initiation (Figure 3). DNA helicase activity and protein mitotic phosphorylation are inversely regulated to ensure proper integration and resetting of the complex activity within the cell cycle (Figures 4 & 5). Finally, the formation of the FACT-MCM complex is associated with cell proliferation and S phase (Figure 6). ND, characteristics of the indicated functional attributes in the quiescent state (or upon exit from cell cycle) have not been determined.