Brazeau - Mitosis Flashcards
Prophase
Chromosomes condense, initial formation of spindles, nuclear envelope breaks down
Metaphase
Spindle microtubules attach to kinetochore, chromosomes align at center of spindles
Anaphase
Sister chromatids separate and move to poles
Telophase
Reformation of nucelar envelope, chromosome decondensation
Checkpoint that must be passed to enter mitosis?
G2 Checkpoint
- DNA Completely synthesized
- No DNA Damage
CDK1/Cyc B
What regulates transition from G2 to M phase?
MPF
CDK1 and Cyclin B
What is the role of MPF?
Once activated, phosphorylates downstream targets responsible for mitosis in positive feedback loop with Aurora Kinase/Polo-like Kinase
- Chromatin Condensation
- Nuclear Envelope Breakdown
- Fragmentation of Golgi
- Spindle formation
What is popular target for cancer drugs in the cell cycle?
Spindle formation in prophase
During DNA replication (S phase), what binds sister chromatids along full length?
(e.g. what maintains linkage of newly synthesized sister chromatids)
Cohesins
What does condensin require to promote condensation of chromatin?
ATP
What drives the shift from cohesin to condensin?
Cyc B, CDK 1, PLKinas
In what phases do each chromosome consist of two sister chromatids until separation at anaphase?
G2 and M
During G2 what holds sister chromatids together along their length?
What occurs during prophase?
Cohesin
Cohesin is removed from most of the length–but stays at the centromere; at the same time condensin begins to condense chromosomes
When are the chromosomes completely condensed?
Metaphase
What initiates nuclear envelope breakdown?
Lamins depolymerize when phosphorylated by MPF (CycB/CDK1)
What works in tandem to push spindle poles apart?
Polar (Inter) and Astral Microtubules
What regulates assembly and disassembly of microtubules?
MAPs
What is the role of the microtubules in chromosome separation?
Ensure alignment and movement of chromosomes
Taxol
Cancer drug which stabilizes microtubules and interferes w/ability to align the chromosome
What special proteins are located at the centromere? What is their purpose?
Histone H3-like Centromeric Protein (CENP)
Bind DNA and kinetochore proteins for attachment of mitotic spindle
What is the protein complex that bind centromere and spindle microtubules?
Kinetochore
What is the equidistant alignment point from both spindles?
Metaphase Plate
What phase is the Spindle Checkpoint?
Metaphase
Mitotic Checkpoint Complex (MCC)
What important protein is part of the complex–and what is its role?
Formed at unattached kinetochores and inhibits APC
Cdc20 – required activator of APC
Once microtubules attach to kinetochore, what happens?
MCC no longer formed; Cdc20 is freed
Free to activate APC (degrade CycB)–trigger anaphase
What event triggers the exit from mitosis?
Degradation of Cyclin B
What is the role of APC?
Ubiquitin Ligase (E3 Enzyme) that makes proteins for degradation by proteosomes.
What are the main targets of APC?
Securin and Cyclin B
Cyclin B destruction inactivates Cdk1
Securin destruction activates Sepase; freeing Cohesin from centromere
What must be completed before Cyclin B is degraded?
What happens when this is not completed?
Chromosome segregation
Nondisjunction; results in aneuploidy
What is the push and pull of chromosome separation?
Push = Polar microtubules via plus end directed motor proteins
Pull = Astra microtubules move spindle toward cell periphery via minus end directed motor proteins
When do Cyclin B levels peak?
What declines with Cyclin B degradation?
What does a decrease in MPF activity permit?
Cyclin B peaks during mitosis
MPF activity, Aurora/PLKinase declin with CycB degradation
Decrease in MPF permits telophase and cytokinesis to proceed
What promotes reassembly of nuclear membrane?
Low kinase activity
Dephosphorylation by Cdc14 Phosphatase
Cleavage Furrow
Perpendicular to long axis of cell, midway between poles
Emits signal for formation of contractile ring
What two proteins pinch off the contractile ring?
Myosin2
Actin
What prevents activation of myosin 2 before anaphase?
What creates environment for activation of myosin II?
What triggers contraction of ring and cytokinesis?
High MPF activity
MPF activity decrease due to APC
Transient increae in intracellular calcium activates MLC kinase
What are the major 2 checkpoints of mitosis?
G2 - complete DNA replication, no DNA damage
Spindle Assembly - All chromosomes have bipolar attachment
What activates APC?
What degrades CycB/CDK1?
CDC20
APC