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Chapter 17 The Cell Cycle. An Overview of the Cell Cycle. 1. The eucaryotic cell cycle is divided into four phases 2. Cell-cycle control is similar in all eucaryotes 3. Cell-cycle control system dissected genetically in yeasts
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Chapter 17 The Cell Cycle
An Overview of the Cell Cycle 1. The eucaryotic cell cycle is divided into four phases 2. Cell-cycle control is similar in all eucaryotes 3. Cell-cycle control system dissected genetically in yeasts 4. Cell-cycle control system analyzed biochemically in animal embryos 5. Cell-cycle progression studied in various ways
Events of eucaryotic cell division as seen under a microscope
Behavior of a temperature-sensitive Cdc mutant room temperature 36°C
Morphology of budding yeast cells arrested by a Cdc mutation Normal yeast cells – buds vary in size according to the cell-cycle stage In a Cdc15 mutant, grown at the restrictive temperature, cells complete anaphase but cannot complete the exit from mitosis and cytokinesis. They arrest uniformly with the large buds, which are characteristic of late M phase
Cell-cycle control system analyzed biochemically in animal embryos A mature Xenopus egg, ready for fertilization
Cell-cycle progression studied in various ways Labeling S-phase cells
The cell-cycle control system 1. Cell-cycle control system triggers the major events of the cell cycle 2. The cell-cycle control system depends on cyclically activated cyclin- dependent protein kinases (Cdks) 3. Inhibitory phosphorylation and Cdk inhibitory proteins (CKIs) can suppress Cdk activity 4. The cell-cycle control system depends on cyclical proteolysis 5. Cell-cycle control also depends on transcriptional regulation 6. The cell-cycle control system functions as a network of biochemical switches
Inhibitory phosphorylation and Cdk inhibitory proteins (CKIs) can suppress Cdk activity The structural basis of Cdk activation
The regulation of Cdk activity by inhibitory phosphorylation
The cell-cycle control system depends on cyclical proteolysis
Cell-cycle control also depends on transcriptional regulation In budding yeast, about 10% of the genes encode mRNAs whose levels oscillate during the cell cycle
The cell-cycle control system functions as a network of biochemical switches
The two central events of the cell cycle are: - replication of DNA during the S phase - chromosome segregation and cell division during the M phase Both these events are controlled by the cyclin-Cdk complexes
S phase 1. S-Cdk initiates DNA replication once per cycle 2. Chromosome duplication requires duplication of chromatin structure 3. Cohesins help hold sister chromatids together
Control of the initiation of DNA replication The ORC remains associated with the ori site throughout the cell cycle. In early G1, Cdc6 and Cdt1 (helicase loading proteins) associate with the ORC and the resulting complex allows the assembly of the Mcm ring and the formation of the prereplicative complex. In the S phase, S-Cdk stimulates the assembly of several additional proteins to form the preinitiation complex. Other proteins are recruited to the origin and replication begins. S-Cdk blocks rereplication by triggering the destruction of Cdc6 and the inactivation of the ORC. The cell is able to assemble the pre-RC only after M-Cdk is inactivated and APC/C is activated at the end of the M-phase
S-Cdk activity is high during G2 and early mitosis. This prevents rereplication from occurring after the S phase M-Cdk also prevents rereplication from occurring during mitosis by phosphorylating the Cdc6 and ORC proteins With all the control elements preventing rereplication, how does DNA replication take place in the next cell cycle? At the end of mitosis, APC/C activation leads to the inactivation of Cdk activity and the destruction of geminin. Pre-RC components are dephosphorylated and Cdt1 is activated allowing pre-RC assembly to initiate a new round of replication
Mitosis • 1. M-Cdk drives entry into mitosis • 2. Dephosphorylation activates M-Cdk at the onset of mitosis • 3. Condensin helps configure duplicated chromosomes for separation • 4. The mitotic spindle is a microtubule-based machine • Centrosome duplication occurs early in the cell cycle • 6. M-Cdk initiates spindle assembly in prophase • 7. The completion of spindle assembly in animal cells requires nuclear envelope breakdown • 8. The APC/C triggers sister-chromatid separation and the completion of mitosis • 9. Unattached chromosomes block sister-chromatid separation: The spindle assembly checkpoint
The APC/C triggers sister-chromatid separation and the completion of mitosis
Mechanism controlling cell-cycle entry and S-phase initiation in animal cells
How DNA damage arrests the cell cycle in G1