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L20 Flashcards

1
Q

what are chromatids

A

the individual replicated chromosomes held together by proteins that allow cohesion

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2
Q

What needs to happen during mitosis?

A

Chromosomes condense

Chromosomes attach to spindle microtubules
- Allow chromosomes to be moved around

Chromosomes align on the spindle

Sister chromatids separated
- Allow chromosomes to be moved into
correct daughter cells

Chromosomes decondense and cell divides into two
- To produce two diploid G1 cells

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3
Q

what are the stages of mitosis

A

prophase

prometaphase

metaphase

anaphase

telophase

cytokinesis

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4
Q

what drives Entry into mitosis

A

M-Cdk (Cyclin B-Cdk1)

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5
Q

how is M-Cdk activated

A

CAK (CDK-activating kinase) phosphorylates a specific threonine residue on M-Cdk

Wee1 adds inhibitory phosphatase keeping M-Cdk inactive

Cdc25 removes inhibitory phosphates added by Wee1. this step activates M-Cdk

active M-Cdk promotes activation of more Cdc25 creating a positive feedback loop

active M-Cdk inhibits Wee1 creating another positive feedback loop

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6
Q

what does M-Cdk do

A
  1. directly phosphorylates key substrate proteins
  2. regulates downstream mitotic kinases (eg Aurora and Polo kinases) which then phosphorylate additional substrates
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7
Q

what is the kinetochore

A

a large macromolecular complex that assembles on the centromere

(the microtubule binding site on a chromosome)

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8
Q

what factors are required to recruit kinetochore proteins in early mitosis

A

M-Cdk (Cyclin B-Cdk1) and Aurora B kinases

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9
Q

how are sister chromatids held together in prophase

A

cohesin proteins

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10
Q

in what stage are cohesins loaded and why

A

G1

to form loops

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11
Q

what releases cohesin first

A

mitotic kinases e.g. polo

leaving some in the center to form X shape

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12
Q

how is the rest of cohesin released

A

via Separase, which cleaves cohesin

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13
Q

how do Chromosomes condense in prophase

A

Condensins I and II co-operate to condense chromosomes in mitosis

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14
Q

what happens to cohesins and condesins in prophase

A

Cohesin removed, Condensins recruited

Interphase chromosome structure lost, mitotic structure gained

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15
Q

summarize what happens in prophase

A

Interphase chromosome structure is lost

Chromosomes condense

Kinetochore assembly begins

Microtubule dynamics change so that the spindle starts to form

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16
Q

what happens in prometaphase

A

Nuclear envelope breaks down
- allows access of microtubules to chromosomes

Spindle assembles

Microtubules attach to chromosomes

Microtubule adapter proteins and motor proteins become active
- allows chromosomes to be moved on the spindle

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17
Q

what is the mitotic spindle

A

A microtubule-based machine required to align and segregate chromosomes

consists of:

  1. interpolar microtubules
  2. astral microtubules
  3. kinetochore microtubules
  4. spindle poles
18
Q

what are the features of microtubules

A

made of tubulin dimers

Nucleated at the minus end

Can grow and shrink at the plus end
(dynamic instability)

19
Q

what proteins are present on microtubules

A

Microtubule adapter proteins (MAPs)

motors

20
Q

what is the function of Microtubule adapter proteins (MAPs) give examples

A

Allow cell components to bind microtubules

Modulate the stability of microtubules

eg Ndc80/Nuf2 at kinetochores

21
Q

what is the function of motors give examples

A

Allow cell components to move along microtubules

eg Kinesin-5 (walks to plus ends)
Dynein (walks to minus ends)

22
Q

give examples of microtubule motors

A

Kinesin-5: forms dimers and cross-links microtubules (cargo is another kinesin-5 molecule)

CENP-E: binds to kinetochores (cargo is a kinetochore)

23
Q

what does kinesin-5 do in prophase

A

cross-links anti-parallel microtubules and pushes them apart

24
Q

what does CENP-E do in prometaphase

A

moves kinetochores towards the cell equator

25
what mechanisms allow for Bi-polarity of the spindle and bi-orientation of chromosomes
Making correct attachments (error correction) Preventing cell cycle progression until suitable attachments are made (spindle checkpoint)
26
what chromosomes are stably attached to microtubules
bi oriented chromosomes
27
what detects bi-orientation
Aurora B kinase localizes to centromeres By a mechanism that it is not fully understood, it detects tension
28
how does Aurora B remove microtubules from kinetochores
Aurora B phosphorylates Ndc80
29
what happens in metaphase
Chromosomes are all bi-oriented As a consequence, they align on the “metaphase plate”
30
what do spindle checkpoints do
If chromosomes are incorrectly attached to the spindle, error correction produces unattached kinetochores The spindle checkpoint detects unattached kinetochores Unattached kinetochores produce the Mitotic Checkpoint Complex (MCC) The MCC inhibits the APC/C and so prevents M-cyclin (Cyclin B) degradation This keeps cells in mitosis Once all kinetochores are occupied with microtubules, the MCC is no longer produced M-cyclin (Cyclin B) is degraded, and the cells “biochemically” exit mitosis Numerous mitotic processes are terminated
31
what proteins are in the MCC
Cdc20 Mad2 BubR1 Bub3
32
how does securin inhibition affect the cell cycle
MCC inhibits APC/C securin is degraded by APC/C securin inhibits seperase, which is a cohesin cleaver in the centromere during metaphase When APC/C is inhibited, securin remains intact, keeping separase inactive. This prevents cohesin cleavage and the premature separation of sister chromatids
33
what happens in Anaphase A
chromosomes move towards the spindle poles
34
what drives anaphase A
Driven largely by microtubule depolymerization at the plus ends of kinetochore microtubules (in human cells)
35
what happens in Anaphase B
spindle poles move apart
36
what drives anaphase B
Driven largely by microtubule motors eg kinesin-5
37
relative importance and timing of anaphase A and B varies between cell types and species
true
38
what happens in telophase
Need to re-establish interphase nuclear and chromosome structure Nuclear envelope reforms, and nuclear pores inserted Chromosomes decondense Condensins dissociate Cohesins re-associate and enable the formation of chromosome looping structures needed for correct gene expression
39
what happens in cytokinesis
A contractile ring of actin and myosin drives cleavage furrow formation and pinching of the dividing cell into two
40
what signals are involved in cytokinesis
From: 1. central spindle 2. spindle poles 3. chromosomes
41
what is the contractile ring made of
actin and myosin

BMS2002 (21 decks)

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