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Review
. 2001 Jan 22;152(2):F11-5.
doi: 10.1083/jcb.152.2.f11.

Nuclear position leaves its mark on replication timing

Affiliations
Review

Nuclear position leaves its mark on replication timing

D M Gilbert. J Cell Biol. .
No abstract available

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Figures

Figure 1
Figure 1
A, Telomere-dependent late replication. yKu binds both telomere DNA and proteins that extend from nuclear pores (Mlp1 and Mlp2; anchored to the pore through NUP145) to mediate the clustering of telomeres at the periphery (for simplicity, only one telomere is shown). yKu and the telomere binding protein Rap1 recruit Sir proteins. The increased local concentration of Sir proteins seeds the propagation of Sir complexes into the adjacent chromatin where they interact with and stabilize hypoacetylated nucleosomes (dark blue N, hypoacetylated; light blue N, acetylated), creating a silenced chromosomal domain. It has been proposed (Dimitrova and Gilbert, 1999; Stevenson and Gottschling, 1999) that such silenced domains set thresholds for the initiation of replication by restricting the access of initiation factors to origin-bound prereplication complexes, consisting of the origin recognition complex (ORC), Cdc6, and the Mcm complex. The nature of the limiting initiation factor(s) is unknown, but is likely to include the B-type cyclin-Cdk (Donaldson et al., 1998b) and Dbf4/Cdc7 (Donaldson et al., 1998a) protein kinases and/or Cdc45 (Aparicio et al., 1999). If the concentration of any one of these initiation factors is limiting at the onset of S phase, initiation would be restricted to those replication origins located within the most accessible domains. As the concentrations of initiation factors increase during S phase, the less accessible later initiating origins can then fire. B, Similar microenvironments may form at multiple sites in mammalian nuclei. See text for details.

Comment on

References

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