Figure 3.

Fox TFs determine the global replication timing program through preferential recruitment of limiting factors, origin clustering, repositioning, and making replication factories. (a) Dbf4-dependent kinase (DDK is recruited to chromosomal arms and pericentromeric origins via Fkh1/2 and Ctf19p-Okp1p-Mcm21p-Ame1p (COMA), respectively. Dbf4 recruitment defines an upstream rate-limiting step in determining replication timing in yeast. A subset of early origins is bound by Fkh1 or Fkh2, which recruits Dbf4 and downstream limiting factors Sld3-Cdc45 in late G1. In pericentromeric origins, Ctf19 recruits DDK to compete for limiting factors. Late or dormant origins need to wait for the cycled use of DDK and other firing factors. (b) Model of Fkh-dependent origin clustering, assemblage of replication components, and formation of replication factories.