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Abstract
In the yeast Saccharomyces cerevisiae DNA replication and spindle assembly can overlap. Therefore, signaling mechanisms modulate spindle dynamics in order to ensure correct timing of chromosome segregation relative to genome duplication, especially when replication is incomplete or the DNA becomes damaged. This review focuses on the molecular mechanisms that coordinate DNA replication and spindle dynamics, as well as on the role of spindle-dependent forces in DNA repair. Understanding the coupling between genome duplication and spindle function in yeast cells can provide important insights into similar processes operating in other eukaryotic organisms, including humans.
Highlights
Spindle formation is a hallmark of mitosis, a mitotic event par excellence
In a textbook view of the cell cycle, events occur in an orderly fashion and S-phase is completed before the G2 phase, in which cells prepare for mitosis
Recent evidence shows that 40% of yeast cells finish telomeric replication at early anaphase, after spindle elongation and chromosome segregation [3]; the same is likely for the replication of the ribosomal DNA (rDNA) locus [17]
Summary
Spindle formation is a hallmark of mitosis, a mitotic event par excellence. In a textbook view of the cell cycle, events occur in an orderly fashion and S-phase is completed before the G2 phase, in which cells prepare for mitosis. These are for example obstacles that prevent progression of replication forks, ranging from cytosine methylation by alkylating agents, to DNA breaks or a lack of dNTPs induced by the drug hydroxyurea (HU) These different types of replication stress are monitored by a checkpoint consisting of early detectors, the ATR kinase Mec and the ATM kinase Tel, that transmit the alert information to the effector kinases Rad, Chk and Dun (Figure 2) [12]. The latter are responsible for orchestrating a cellular response that includes chromosome segregation arrest, upregulation of dNTP pools, activation of DNA damage response genes, suppression of late replication origin firing and stabilization of the replication forks. To what extent are DNA replication and spindle function coordinated in yeast cells?
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