The chromosome cycle: coordinating replication and segregation. Second in the cycles review series

Abstract

During the cell-division cycle, chromosomal DNA must initially be precisely duplicated and then correctly segregated to daughter cells. The accuracy of these two events is maintained by two interlinked cycles: the replication licensing cycle, which ensures precise duplication of DNA, and the cohesion cycle, which ensures correct segregation. Here we provide a general overview of how these two systems are coordinated to maintain genetic stability during the cell cycle.

Figure 1

Overview of the licensing and cohesion cycles. A small segment of chromosomal DNA, encompassing three replication origins, is shown during G1, S and G2. Mcm2–7 and cohesin are loaded during G1. During S phase, the Mcm2–7 complex is displaced from DNA as it replicates, and cohesion is established. During anaphase, cohesin is cleaved, thereby allowing segregation of sister chromatids.

Figure 2

Components of the pre-replicative complex. The licensing of a single replication origin is shown. ORC is first recruited to chromatin, and then recruits Cdc6 and Cdt1. The ORC–Cdc6–Cdt1 complex licenses the origin by loading numerous Mcm2–7 complexes onto it.

Figure 3

The cohesin cycle. During telophase or G1, cohesin loading depends on Scc2 and Scc4. During S phase, establishment of cohesion requires Ctf18, Eco1 and other proteins, as well as cohesin. At the onset of anaphase, APC/C–Cdc20 promotes degradation of securin, thereby activating separase, which cleaves cohesin.

Figure 4

Ensuring sister kinetochore bi-orientation. In the absence of the tension across sister kinetochores, Aurora B kinase (called Ipl1 in budding yeast) destabilizes the interaction between microtubules and kinetochores (left). Once bi-orientation is established, tension across the kinetochores (dependent on the presence of cohesion) stabilizes the microtubule–kinetochore interaction (right).