Mitosis Flashcards
(36 cards)
1
Q
What are the stages of mitosis?
A
- Interphase (pre)
- Prophase
- Prometaphase
- Metaphase
- Anaphase
- Telophase
- Cytokinesis (post)
2
Q
Interphase
A
- Before mitosis
- Nuclear envelope intact
- No visible chromosomes
3
Q
Prophase
A
- Chromosomes condense and become visible
- Bipolar spindle develops
4
Q
Prometaphase
A
- Nuclear envelope dissolves
- Chromosomes begin to migrate to the metaphase plate
- 2 chromatids visible
5
Q
Metaphase
A
- Chromosomes fully condensed and at metaphase plate
6
Q
Anaphase
A
- Each centromere splits
- 2 chromatids of each chromosome are pulled to opposite poles
7
Q
Telophase
A
- Chromosomes reach poles and start to decondense
- Nuclear membrane reforms
- Cytoplasm begins to divide
8
Q
Cytokinesis
A
- Cytoplasm division completed resulting in 2 daughter cells
9
Q
How is the genome organized during interphase?
A
- DNA double helices are wrapped around histones
- Nucleosomes are coiled into a chromatin fiber
10
Q
What are the two structural maintenance complexes (SMC)?
A
- Related complexes that organize chromosomes during mitosis
- Elongated coil-coil ATPases
11
Q
Cohesin
A
- 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
12
Q
Condensin
A
- An SMC
- Compacts chromosomes: uses ATP to pump a loop of DNA through itself creating a more compact chromosome structure
- Organizes for efficient segregation
13
Q
What is the role of topoisomerase in mitosis?
A
- Topoisomerase decatenates and relaxes supercoils, helping with chromosome compaction
14
Q
What is the role of histone phosphorylation in mitosis?
A
Chromosome compaction
15
Q
How are the mitotic cyclins activated?
A
- 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
16
Q
How is mitotic cyclin activation regulated?
A
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
17
Q
How does the nuclear envelope disassemble during prophase/prometaphase and reassemble during telophase?
A
- Phosphorylation of nuclear pore proteins and lamins => membrane disassembly. Nuclear envelope forms vesicles.
- Dephosphorylation allows for reassembly around the daughter chromosomes.
18
Q
What elements make up the structure of the nuclear envelope?
A
- Inner and outer nuclear membranes contiguous with ER
- Nuclear pores
- Lamins = intermediate filaments inside the inner membrane for structure and organization
19
Q
What are the structure and function of the kinetochore?
A
- 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.
20
Q
How do microtubule spindles form?
A
- Grow outward from centrosome attachments in a - => + direction via dynamic instability
21
Q
What are the functions of molecular motors in mitosis?
A
- Spindle formation
- MT dynamics
- Chromosome alignment
22
Q
What are kinesin and dyenin?
A
- Kinesin = + end directed molecular motor (away from centromere)
- Dyenin = - end directed molecular motor (towards centromere)
23
Q
What microtubule structures are present in the dividing cell?
A
- Aster microtubules: branch out from spindle pole
- Kinetochore microtubules: bind to kinetochores
- Interpolar microtubules: associate with microtubules from opposite pole
24
Q
What does the mitotic checkpoint check for?
A
All chromosomes must be attached to mitotic spindle
25
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
26
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
27
What is APC/C and what are its targets?
An E3 ubiquitin ligase targeting cyclinB-Cdk-1 and securin
28
What are microtubule poisons used to treat?
Cancer, via MT breakdown or inhibition of MT dynamics
29
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
30
Cytokinesis
- Actin-myosin ring forms at equator (as per signals from the spindle-cortex interactions and spindle midzone)
- Contractile ring constricts
31
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)
32
What is aneuploidy?
Having too many or too few chromosomes
33
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
34
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
35
What is anaphase lag?
- caused by merotelic attachment of kinetochores => aneuploidy and micronuclei (lone chromatid gets a mini nucleus with incomplete machinery)
36
What are chromosome bridges?
- a chromosome segregation error caused by fused sister chromatids entering mitosis => aneuploidy
