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BMS2002 > L20 > Flashcards

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
Q

what mechanisms allow for Bi-polarity of the spindle and bi-orientation of chromosomes

A

Making correct attachments (error correction)

Preventing cell cycle progression until suitable attachments are made (spindle checkpoint)

26
Q

what chromosomes are stably attached to microtubules

A

bi oriented chromosomes

27
Q

what detects bi-orientation

A

Aurora B kinase localizes to centromeres

By a mechanism that it is not fully understood, it detects tension

28
Q

how does Aurora B remove microtubules from kinetochores

A

Aurora B phosphorylates Ndc80

29
Q

what happens in metaphase

A

Chromosomes are all bi-oriented
As a consequence, they align on the “metaphase plate”

30
Q

what do spindle checkpoints do

A

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
Q

what proteins are in the MCC

A

Cdc20

Mad2

BubR1

Bub3

32
Q

how does securin inhibition affect the cell cycle

A

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
Q

what happens in Anaphase A

A

chromosomes move towards the spindle poles

34
Q

what drives anaphase A

A

Driven largely by microtubule depolymerization at the plus ends of kinetochore microtubules (in human cells)

35
Q

what happens in Anaphase B

A

spindle poles move apart

36
Q

what drives anaphase B

A

Driven largely by microtubule motors eg kinesin-5

37
Q

relative importance and timing of anaphase A and B varies between cell types and species

A

true

38
Q

what happens in telophase

A

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
Q

what happens in cytokinesis

A

A contractile ring of actin and myosin drives cleavage furrow formation and pinching of the dividing cell into two

40
Q

what signals are involved in cytokinesis

A

From:

  1. central spindle
  2. spindle poles
  3. chromosomes
41
Q

what is the contractile ring made of

A

actin and myosin

BMS2002 (21 decks)

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