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Biomed Season Finale > Health and Disease - Cell Division > Flashcards

Health and Disease - Cell Division Flashcards

1
Q

what occurs during prophase

A

condensation of replicated chromosomes
centrosomes migrate away from eachother

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2
Q

what occurs during prometaphase

A

nuclear membrane retraction
kinetichores form on centrosomes to attach to spindle fibers

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3
Q

what occurs during metaphase

A

chromosome positioning on the metaphase plate in the centre of the spindle

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4
Q

what occurs during anaphase

A

separation of sister chromatids of each duplicated chromosome towards the spindle poles

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5
Q

what occurs during telophase

A

mitotic spindle disassembly
nuclear envelope reformation

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6
Q

structure and features of the mitotic spindle

A

microtubules are polarised
MT assembly is initiated at the - end
+ end is where most growth occurs
search for chromosomes via dynamic growth cycles

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7
Q

what does each centrosome consist of

A

a cloud of amorphous material around the pair of centrioles
pericentriolar matrix

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8
Q

what happens in the pericentriolar matrix

A

Microtubules nucleate projecting their fast-growing
plus-ends outward while their minus-ends
associated with the centrosome

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9
Q

function of microtubule associated coiled-coil proteins

A

link motor proteins to the centrosome
localise components of the cell-cycle control system

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10
Q

function of γ-tubulin ring complexes

A

drives microtubule nucleation

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11
Q

function and features of kinesin-5

A

two plus-end motor domains, which move on antiparallel microtubules in the
spindle mid-zone => pole separation by sliding antiparallel microtubules

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12
Q

function/features of kinesin-14

A

one minus-end motor domain, and can cross-link antiparallel interpolar
microtubules at the spindle mid-zone => pull the poles together.

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13
Q

function and features of kinesin 10/4

A

plus-end directed motors that associate with chromosome arms
=> push the attached chromosome away from the pole

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14
Q

features and function of dyneins

A

minus-end directed motors on astral microtubules => pull the spindle poles toward
the cell cortex and away from each other

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15
Q

what is a kinetichore

A

e is a multi-protein structure (50
different proteins) at the centromeric region of the
chromatid

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16
Q

function of the + end of kinetichore microtubules

A

bind to the outer site of the kinetichore

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17
Q

what is kinetochore microtubule attachment reliant on

A

Ndc80

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18
Q

function of Ndc80

A

maintains integrity of microtubule-binding sites of the kinetochore

controls kinetochore microtubules
dynamics by promoting local polymerization and
depolymerization of their plus-ends

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19
Q

function of cohesins

A

ring like proteins that hold together chromosomes at their centrosomes

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20
Q

what occurs once spindle-assembly checkpoint processes have been satisfied

A

Cdc20 triggers sister chromatid separation

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21
Q

function of Cdc20

A

activates the APC/C (anaphase-promoting complex/cyclosome) ubiquitin
ligase which polyubiquitinates a protein called securin

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22
Q

function of securin

A

inhibitor of separase

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23
Q

what happens once securin is degraded by proteosomes

A

separase cleaves the Scc1 component of cohesins resulting in their disassembly and separation of sister chromatids to the spindle poles

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24
Q

what is non-disjunction

A

chromosomes segregate in anaphase prior to attachment of the
kinetochores of all sister chromatids to mitotic spindle fibers.

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25
Q

how is non-disjunction prevented

A

Mad2 (mitotic arrest
deficient 2) and Bub1 complex which is known as the
spindle-assembly checkpoint (SAC) operates just prior
to anaphase
Mad2 binds to kinetochores that have not bound to
microtubules of the mitotic spindle
* Kinetochore binding activates Mad2, and inhibits the
activity of Cdc20 which controls the APC/C ubiquitin
ligase
* This delays degradation of securin and anaphase.

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26
Q

what increases the production of reactive oxygen species and what does it cause

A

Energy
proteotoxic and other aneuploidy associated stresses
activates p53 via ATM

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27
Q

what is are the courses of action p53 may take depending on the level of aneuploidy

A

cell cycle arrest
apoptosis

28
Q

what is the LGN complex

A

an evolutionary conserved cortical force generator which orients the mitotic spindle

29
Q

how is temporal and spatial regulation of LGN complex achieved

A

LGN protein expression increases during mitosis
restricts LGN complex formation to mitosis

30
Q

function of chromatin-associated guanine nucleotide
exchange factor (GEF)

A

stimulates Ran (Ras-related nuclear) GTPase

31
Q

function of Ran GTPase

A

restricts LGN localization to two
cortical crescents facing the spindle poles during
metaphase (and anaphase)

32
Q

features and function of Polo-like kinase 1 (Plk1)

A

localized at the spindle poles
phosphorylates and negatively controls the cortical localization of dynein

33
Q

what does the specific localization of the LGN complex determine

A

the site of force concentration on
astral microtubules and the axis of spindle orientation

34
Q

what does the LGN complex direct and what does it cause

A

the recruitment of the minus-end-directed microtubule motor dynein
* The directed movement of dynein along astral microtubules generates pulling forces on the
spindle poles leading to the orientation and/or positioning of the spindle

35
Q

how will cells orient their mitotic spindles

A

along their longest axis

36
Q

what is the feature of an unpolarised cell

A

all the polarity components such as ECM are evenly localised throughout the cell

37
Q

what are the steps for the establishment of cell polarity

A

1 - breaking symmetry via extrinsic cues/stochastically
2 - establishing spatial organisation via signallling transduction
3 - amplifying and maintaining polarity via feedback loops

38
Q

what are the features of the crumb complex

A

an evolutionary conserved module
localised at the apical domain
Scaffold proteins associated with Pals1 and PATJ

39
Q

what are the features of the Par complex

A

evolutionary conserved proteins to establish polarity including:
- Par3/6
- Cdc42
- aPKC

40
Q

what are the features of the basolateral Scribble complex

A

evolutionary conserved module containing:
- Lgl
- Scribble
- Dlg

41
Q

what does Par3 localise to

A

adherins junctions

42
Q

what does Par1 phosphorylate, causing what

A

phosphorylates Par3
phosphorylated Par3 associates with Par5
leads to their cytoplasmic sequestration

43
Q

what does Par3 help recruit

A

helps recruit E-cadherins to establish adherin junctions

44
Q

what does activated Par3/Cdc42 recruit

A

they recruit Par6 and aPKC to the cortex
Par3 also recruits Par1

45
Q

what occurs at stage 3 of polarity establishment

A

aPKC phosphorylates Par3
restricts Par3 to more basal location above adherin junctions
contributes to apical-lateral border

46
Q

what occurs at stage 4 of polarity establishment

A

aPKC phosphorylation of Par3 disrupts the Par3-Pal1 interactions
Pal1 begins to stabilise Crumbs in the apical domain

47
Q

how is cell polarity maintained

A

Par6-aPKC and scribble complexes maintain polarity through reciprocal inhibition

48
Q

what is the effect of Par3 silencing

A

dramatically reduced tumour latency in mouse models of breast cancer
enhanced tumour growth

49
Q

what is Par3 depletion associated with

A

induction of MMP9
destruction of ECM
invasion

50
Q

how is Par3 expression affected in breast cancer

A

expression is significantly reduced
correlates with active aPKC and Stat3

51
Q

what is MDM2

A

it is the E3 ubiquitin ligase of p53 that controls p53 levels via proteosomal degradation

52
Q

structural features of MDM2

A

self destructive RING-finger-containing ubiquitination enzyme

53
Q

what is Nutlin3a

A

small molecule that binds to MDM2’s p53 binding domain to disrupt the MDM2-p53 complex

54
Q

what is HIL98

A

a small molecule that binds to MDM2 to inhibit the E3 ligase activity at the carboxyl terminus

55
Q

what is RITA

A

a small molecule that blocks the MDM2-p53 complex by binding to p53

56
Q

how is guidance of microtubule growth ordained

A

actin-microtubule crosslinking proteins associate with microtubules via +TIPS
provides dynamic link between actin and microtubules
regulates microtubule growth

57
Q

how is anchoring and stabilization of microtubules achieved

A

protein complex associated with the cortical actin networks captures both the + and - minus ends of microtubules

58
Q

what does actin form at the basal end

A

forms a membrane bound cortex along the cell wall
also forms a contractile belt on the apical face of the cortex

59
Q

what is the apical-basal polarity maintained by

A

regulated interactions with the +/- ends of microtubules and the actin cortex at the basal and apical surfaces respectively

60
Q

what are the minus ends of microtubules anchored by

A

actin crosslinking family protein 7 (ACSF7)
and
microtubule minus-end tracker calmodulin- regulated spectrin associated protein 3
(CAMSAP3)

61
Q

what are the plus ends of microtubules anchored by

A

anchored by membrane bound LL5alpha/LL5beta in the presence of active integrins
this is done through end binding proteins (EB’s) and the cytoplasmic linker associated proteins (CLASP2)

62
Q

what are microtubule minus ends captured by

A

captured by CAMSAP3 which interacts with p120-catenin
this is done through PLEKHA7

63
Q

what are microtubule plus ends captured by

A

captured by +TIPs that interact with adherins junction’s via beta-catenin and p120-catenin

64
Q

how do microtubules promote junction formation

A

delivering junction components
promoting recruitment and activation of myosin II - drives clustering of E-cadherins

65
Q

function of kinesin KIF17 localised at microtubules plus ends

A

activates RHOA
promotes accumulation of junctional actin and adhesion stability

66
Q
A

Biomed Season Finale (11 decks)

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