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Foundations 1 > Mitosis > Flashcards

Mitosis Flashcards

1
Q

What are the stages of mitosis?

A
  • Interphase (pre)
  • Prophase
  • Prometaphase
  • Metaphase
  • Anaphase
  • Telophase
  • Cytokinesis (post)
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2
Q

Interphase

A
  • Before mitosis
  • Nuclear envelope intact
  • No visible chromosomes
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3
Q

Prophase

A
  • Chromosomes condense and become visible

- Bipolar spindle develops

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4
Q

Prometaphase

A
  • Nuclear envelope dissolves
  • Chromosomes begin to migrate to the metaphase plate
  • 2 chromatids visible
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5
Q

Metaphase

A
  • Chromosomes fully condensed and at metaphase plate
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6
Q

Anaphase

A
  • Each centromere splits

- 2 chromatids of each chromosome are pulled to opposite poles

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7
Q

Telophase

A
  • Chromosomes reach poles and start to decondense
  • Nuclear membrane reforms
  • Cytoplasm begins to divide
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8
Q

Cytokinesis

A
  • Cytoplasm division completed resulting in 2 daughter cells
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9
Q

How is the genome organized during interphase?

A
  • DNA double helices are wrapped around histones

- Nucleosomes are coiled into a chromatin fiber

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10
Q

What are the two structural maintenance complexes (SMC)?

A
  • Related complexes that organize chromosomes during mitosis

- Elongated coil-coil ATPases

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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
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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
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13
Q

What is the role of topoisomerase in mitosis?

A
  • Topoisomerase decatenates and relaxes supercoils, helping with chromosome compaction
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14
Q

What is the role of histone phosphorylation in mitosis?

A

Chromosome compaction

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15
Q

How are the mitotic cyclins activated?

A
  1. M-cyclin (cyclinB) binds Cdk-1 forming an inactive M-Cdk complex
  2. Cdk-activating kinase (CAK) and Cdk-inhibitory kinase (Wee1) phosphorylate M-Cdk, which remains inactive
  3. Phosphatase (Cdc25) removes the inhibitory phosphate and M-Cdk is activated
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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
Q

What happens if spindle assembly is not complete at the mitotic checkpoint?

A
  • Unattached kinetochore induces the mitotic checkpoint complex (MCC)
  • MCC inhibits APC, which is required for anaphase progression
26
Q

What does APC activation after metaphase cause?

A
  • 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
Q

What is APC/C and what are its targets?

A

An E3 ubiquitin ligase targeting cyclinB-Cdk-1 and securin

28
Q

What are microtubule poisons used to treat?

A

Cancer, via MT breakdown or inhibition of MT dynamics

29
Q

Compare anaphase A and anaphase B.

A

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
Q

Cytokinesis

A
  • Actin-myosin ring forms at equator (as per signals from the spindle-cortex interactions and spindle midzone)
  • Contractile ring constricts
31
Q

What are some types of errors in chromosome kinetochore attachment?

A
  • 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
Q

What is aneuploidy?

A

Having too many or too few chromosomes

33
Q

What are some types of errors in chromosome segregation?

A
  • SAC mutations
  • premature loss of chromatid cohesion
  • aberrant kinetochore attachments
  • supernumary centrosomes: extra centrosome means cell is split with > 2 poles => tumorigenesis
34
Q

What are trisomies and how are they tolerated?

A
  • 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
Q

What is anaphase lag?

A
  • caused by merotelic attachment of kinetochores => aneuploidy and micronuclei (lone chromatid gets a mini nucleus with incomplete machinery)
36
Q

What are chromosome bridges?

A
  • a chromosome segregation error caused by fused sister chromatids entering mitosis => aneuploidy

Foundations 1 (26 decks)

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