Chap 17 - Cell cycle regulation I Flashcards
What are Cdks?
Cyclin dependent kinases. Protein kinases that are a central component of the cell-cycle control system.
What does an increase in Cdk activity in G2/M transition mean for the cell?
Results in an increase in phosphorylation of proteins that control chromosome condensation, nuclear-envelope breakdown, spindle assembly
What regulates Cyclin dependent kinases?
Proteins known as cyclins. Depend on cyclin for activity. No cyclin –> no kinase activity.
Name the four classes of cyclins, their function, and at what stage they bind/activate Cdks.
G1/S-cyclins: late G1 phase, trigger progression through Start - commiting to cell-cycle entry. S-cyclins: soon after progression through Start, stimulate chromosome duplication M-cyclins: G2/M transition, stimulate entry into mitosis’ G1-cyclins: govern activity of G1/S cyclins
Name the order in which the phases of mitosis occur
PPMAT Prophase - Prometaphase - Metaphase - Anaphase - Telophase
Explain the phases of mitosis - PPMAT
Prophase: Chromosomes condense, mitotic spindle forms, nucleolus disappears Prometaphase - late prophase: Chromosomes even more condensed, nuclear envelope breaks down - releases chromosomes, mitotic spindle grows, microtubules capture chromosomes Metaphase: Chromosomes align, kinetochores are attached to microtubules from opposite spindles poles Anaphase: Protein holding sister chromatids together breaks down - they separate, microtubules let go - separating the poles elongating the cell Telophase: Mitotic spindle breaks down, 2 new nuclei form, chromosomes de-condense
How can you visualize the cell cycle and its stages?
Staining with DNA-binding fluorescent dye, staining with antibodies that recognize specific cell components (ex. microtubules), measure DNA content - flow cytometry
Explain the 3 major regulatory transitions in the cell-cycle control system.
1) Start - restriction point - in late G1. The cell commits to cell-cycle entry and chromosome duplication. 2) G2/M transition. Control system triggers early mitotic events that lead to chromosome alignment on mitotic spindle in metaphase 3) Metaphase-to-anaphase transition. Control system stimulates sister-chromatid separation, leading to completion of mitosis and cytokinesis.
What is cytokinesis?
The physical process of the cell dividing.
What does the protein kinase Wee1 do?
Phosphorylate kinase active site which inhibits Cdk activity.
What does the phosphatase Cdc25 do?
Dephosphorylate kinase active sites which increases Cdk activity.
What does Cdk inhibitor proteins (CKIs) do?
They inactive cyclin-Cdk complexes. Cells use them to help govern the activities of G1/S- and S-Cdks early in the cell cycle.
Explain the function of anaphase-promoting complex (APC/C or cyclosome)
A key regulator of metaphase-to-anaphase transition. Member of ubiquitin ligase enzyme-family. Stimulate degradation of specific regulatory proteins.
Can mitosis occur without cytokinesis? Explain.
Yes, some cells can undergo multiple rounds of nuclear division without undergoing the physical dividing. After nuclear division, membranes are created around each nucleus - cellularization. The plasma membrane extends inward and actin-myosin ring encloses each nucleus.
APC/C (cyclosome) catalyzes the destruction of what proteins?
Securin: Protects protein linkages between sister chromatids. Destruction of securin activates a protease that separates the sisters and start anaphase. S- and M-cyclins: Destruction of these inactives most Cdks in the cell.
Explain the function and control of SCF ubiquitin ligase.
Ubiquitylate certian CKI proteins in late G1 - helping control the activiation of S-Cdks and DNA replication. Depends on substrate-binding subunits F-box proteins. Activity is constant during the cell cycle. Ubiquitylation by SCF is controlled by changes in phosphosrylation state of its targets proteins.
Explain the control of ACP/C.
Activity changes during the cell cycle. Depends on Cdc20 and Cdh1 subunits to recognize target proteins.
Give an overview of the cell control system.
G1/S-Cdks unleash S-Cdk activity –> chromosome duplication in S phase –> M-CDk activation triggers progression through G2/M transition –> alignment of sister-chromatid pairs –> APC/C + Cdc20 triggers destruction of securin and cyclins –> sister chromatid separation - completion of mitosis
Where does DNA replication begin?
Origins of replication
How is DNA replication initiated?
On origin of replication, when a DNA helicase unwinds the double helix of DNA and replication enzymes are loaded onto the two single stranded templates.
How is DNA replication initiated?
On origin of replication, when a DNA helicase unwinds the double helix of DNA and replication enzymes are loaded onto the two single stranded templates. This leads to elongation, where the replication machinery moves outward from origin at 2 replications forks.
The initiation phase of DNA replication is divided into 2 steps - which?
1) In late mitosis/early G1 phase - pair of inactive DNA helicases is loaded onto the replication origin, forming the pre-replicative complex (preRC) 2) In S phase - DNA helicases are activated, which results in DNA unwinding and initiation of DNA synthesis
Explain the role of cohesins
Large protein complex. They form ring like structures. Plays a part in the cohesion of sister chromatids, at the end of S phase.
What is a syncytium?
A cell with multiple nuclei in the cytoplasma.
