Mitosis Flashcards
What are the stages of mitosis?
- Interphase (pre)
- Prophase
- Prometaphase
- Metaphase
- Anaphase
- Telophase
- Cytokinesis (post)
Interphase
- Before mitosis
- Nuclear envelope intact
- No visible chromosomes
Prophase
- Chromosomes condense and become visible
- Bipolar spindle develops
Prometaphase
- Nuclear envelope dissolves
- Chromosomes begin to migrate to the metaphase plate
- 2 chromatids visible
Metaphase
- Chromosomes fully condensed and at metaphase plate
Anaphase
- Each centromere splits
- 2 chromatids of each chromosome are pulled to opposite poles
Telophase
- Chromosomes reach poles and start to decondense
- Nuclear membrane reforms
- Cytoplasm begins to divide
Cytokinesis
- Cytoplasm division completed resulting in 2 daughter cells
How is the genome organized during interphase?
- DNA double helices are wrapped around histones
- Nucleosomes are coiled into a chromatin fiber
What are the two structural maintenance complexes (SMC)?
- Related complexes that organize chromosomes during mitosis
- Elongated coil-coil ATPases
Cohesin
- An SMC
- Keeps sister chromosomes together during segregation of metaphase and ensures ones sister chromatid ends up in each daughter cell
- Load before replication (G1) and maintained through metaphase
- Dissolution of cohesion during anaphase
Condensin
- An SMC
- Compacts chromosomes: uses ATP to pump a loop of DNA through itself creating a more compact chromosome structure
- Organizes for efficient segregation
What is the role of topoisomerase in mitosis?
- Topoisomerase decatenates and relaxes supercoils, helping with chromosome compaction
What is the role of histone phosphorylation in mitosis?
Chromosome compaction
How are the mitotic cyclins activated?
- M-cyclin (cyclinB) binds Cdk-1 forming an inactive M-Cdk complex
- Cdk-activating kinase (CAK) and Cdk-inhibitory kinase (Wee1) phosphorylate M-Cdk, which remains inactive
- Phosphatase (Cdc25) removes the inhibitory phosphate and M-Cdk is activated
How is mitotic cyclin activation regulated?
Positive feedback:
- active M-Cdk inhibits Wee1 inhibitory kinase
- active M-Cdk activates Cdc25 phosphatase
G2/M DNA damage checkpoint:
- Via a signaling cascade, DNA damage causes Cdc25 export from the nucleus
- M-Cdk will not be activated
How does the nuclear envelope disassemble during prophase/prometaphase and reassemble during telophase?
- Phosphorylation of nuclear pore proteins and lamins => membrane disassembly. Nuclear envelope forms vesicles.
- Dephosphorylation allows for reassembly around the daughter chromosomes.
What elements make up the structure of the nuclear envelope?
- Inner and outer nuclear membranes contiguous with ER
- Nuclear pores
- Lamins = intermediate filaments inside the inner membrane for structure and organization
What are the structure and function of the kinetochore?
- Interface between chromosome and MT spindle that controls all chromosome movement
Different structural elements:
- Centromeric chromatin: histones
- Inner kinetochore: associated with centromere DNA, present throughout the cell cycle
- Outer kinetochore: associates with MTs (via various proteins), dynamic and only present during mitosis.
How do microtubule spindles form?
- Grow outward from centrosome attachments in a - => + direction via dynamic instability
What are the functions of molecular motors in mitosis?
- Spindle formation
- MT dynamics
- Chromosome alignment
What are kinesin and dyenin?
- Kinesin = + end directed molecular motor (away from centromere)
- Dyenin = - end directed molecular motor (towards centromere)
What microtubule structures are present in the dividing cell?
- Aster microtubules: branch out from spindle pole
- Kinetochore microtubules: bind to kinetochores
- Interpolar microtubules: associate with microtubules from opposite pole
What does the mitotic checkpoint check for?
All chromosomes must be attached to mitotic spindle
What happens if spindle assembly is not complete at the mitotic checkpoint?
- Unattached kinetochore induces the mitotic checkpoint complex (MCC)
- MCC inhibits APC, which is required for anaphase progression
What does APC activation after metaphase cause?
- proteolysis of mitotic cyclins (cyclinB-Cdk1)
- loss of chromosome cohesion (via proteolysis of securin, which inhibits separase, which degrades cohesin)
- separation of sister chromatids
What is APC/C and what are its targets?
An E3 ubiquitin ligase targeting cyclinB-Cdk-1 and securin
What are microtubule poisons used to treat?
Cancer, via MT breakdown or inhibition of MT dynamics
Compare anaphase A and anaphase B.
A:
- forces generated mainly at kinetochores
- kinetochore MTs shorten via depolymerization with kinetochores holding on to the shortening ends
- daughter chromosomes move towards the poles
B:
- forces involve molecular motors
- interpolar MTs elongate pushing poles apart
- kinesin-14 and -5 walk along + ends of spindle MTs and generate a sliding force pushing poles apart
- dyneins bind plasma membrane and pull poles apart
Cytokinesis
- Actin-myosin ring forms at equator (as per signals from the spindle-cortex interactions and spindle midzone)
- Contractile ring constricts
What are some types of errors in chromosome kinetochore attachment?
- Amphitelic = success
- Syntelic = both kinetochores attached to one pole
- Monotelic = only one kinetochore attached to one pole
- Merotelic = one extra MT attaches to one kinetochore (3/4 or 4/4 sisters may end up in one cell)
What is aneuploidy?
Having too many or too few chromosomes
What are some types of errors in chromosome segregation?
- SAC mutations
- premature loss of chromatid cohesion
- aberrant kinetochore attachments
- supernumary centrosomes: extra centrosome means cell is split with > 2 poles => tumorigenesis
What are trisomies and how are they tolerated?
- Missegregation of chromosomes during meiosis I or II leading to an extra copy of a chromosome.
- Tolerated: 13, 18, 21, X, and Y
- Miscarriage: 15, 16, 22
- Not tolerated: 1-12, 14, 17, 19, 20
What is anaphase lag?
- caused by merotelic attachment of kinetochores => aneuploidy and micronuclei (lone chromatid gets a mini nucleus with incomplete machinery)
What are chromosome bridges?
- a chromosome segregation error caused by fused sister chromatids entering mitosis => aneuploidy
