Week 5 Cell Division and Death- Holy Flashcards Preview

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Flashcards in Week 5 Cell Division and Death- Holy Deck (47):
1

What happens in interphase?

cell increases size, DNA is replicated, centrosome is duplicated. Contains G1, S, and G2 phases

2

What happens in G1 Phase?

Cells monitor environmental surroundings, decide to remain in cycle or stop dividing. Contains Restriction/ Start point, if passed cells are committed to initiating DNA synthesis and entering mitosis
*Mitogen binds receptor
*Ras is activated
*MAP cascade
*MAP enters nucleus and activates TF
*Early genes (Myc_
*Late genes (CYCLIN D)
*Cyclin D + Cdk phosphorylates retinoblastoma protein (Rb) which releases EF2
*Active EF2 turns on genes for S phase initiation like cyclins E and A

3

S phase

DNA synthesis
Centrosome replicates and moves apart
Produces chromatids that remain connects and centromere by cohesins.

4

G2 phase

gradually merges into M-phase
Chromosomes being to condense in preparation
Point at which condensation is visible in microscope starts M-phase

5

Cohesin

protein complexes that hold replicated chromosomes (chromatids) together until the can be accurately seperated by spindle apparatus.

6

Define M-phase (mitosis)

process by which replicated chromosomes are segregated. Contains prophase, prometaphase, metaphase, anaphase, telophase,

7

Prophase

sister chromatids condense by condensins
outside nucleus mitotic spinde assembles between the two centrosomes

8

prometaphase

break down of nuclear envelope, chromosomes attach to spindle microtubules via kinetochores

9

Centromeric heterochromatin

centromeres contain special histone H3 variant (CENP-A), chromatin in this region is TIGHTLY compacted to form scaffolding for assembly of protein complexes that form the kinetochores

10

What are the three types of forces working on kinetochores?

Kinetochore microtubules- pull kinetochore toward pole, which orients chromatid (pulls them apart in anaphase)
Interpolar microtubules- push chromosomes away from poles (aligns them on plate)
Astral microtubules- push chromosomes away from pole (helps align them on plate)

11

Metaphase

chromosomes are aligned in the middle, kinetochore microtubules attach sister chromatids to opposite poles of the spindle.

12

What forces help microtubules line up sister chromatids on metphase plate?

Microtubule polymerization and depolymerizaiton
interaction of microtubules with actin and myosin in the cell cortex
activities of dynein and multiple kinesins

13

Anaphase

sister chromatids seperate to form two daughter chromosomes and are pulled toward spindle pole through kinetochore microtubules getting shorter AND movement of spindle poles

14

Telophase

two sets of daughter chromosomes arrive at spindle poles and decondense. Nuclear envelope reassembles around each set. Formation of two nuclei

15

Cytokinesis

Cytoplasm is divided in two by contractile ring of actin and myosin filaments controlled by Rho, pinches into 2 daughter cells

16

What proteins drive the cell cycle?

CDKs, Cyclin, and CKIs

17

How are CDKs regulated?

binding with cyclin activates the kinase funciton
Phosphorylation pattern (has activating phosphate and doesn't have inhibitory phosphate)
CKIs- able to bind to the cyclin-CDK complex and block kinase activity of the Cdk

18

What do you need to maintain cyclin D levels?

short half life, need continues growth factor signaling

19

What shuts off G1-Cdk activity?

stimulation stops

20

Describe pre-RC complex

pre-RC complex forms in early G1 soon after completely M-phase
initiator proteins bind to the origins of replication to make pre-replication complex
**NOTE** pre-RC proteins can only bind when UNPHOSPHORYLATED- they are substrates for Cdks so can only form pre-RC when there is low Cdk activity (Right after mitosis)

21

What are important functions of S-Cdks?

once activated recruits more proteins to pre-RC to form the pre-initiation complex. This unwinds DNA and begins synthesis.
**S-Cdks phosphorylate, dissociate, and degrade pre-RC proteins** thus DNA can be replicated ONCE and only ONCE.

22

Describe M-Cdk activity

(Cdk1/Cyclin B complex formed in S phase)- responsible for driving MITOSIS. Targets:
Condensins: Chromosome condensation
Nuclear pore complexes and lamins: nuclear envelope breakdown
Centrosomal proteins: mitotic spindle formation
Proteins assosiate with Golgi and ER: fragmentation of Golgi and ER

23

What roles do Wee1, CAK and Cdc25 play?

Wee1- inhibitory kinase of M-Cdk
CAK- activating kinase of M-Cdk
*inhibitory phosphorylation keeps M-Cdk activity low.
Cdc25- removes inhibitory phosphate, activating M-Cdk

24

Two examples of positive feedback in M-Cdk regulation

1. M-Cdk activates Cdc25 promoting activation of more M-Cdk
2. M-Cdk phosphorylates Wee1 (inactivating it) which promotes more M-Cdk activation

25

What does the APC do?

Anaphase promoting complex
activated by M-Cdk
ubiquinates proteins for proteolysis.
Targets:
Securin- inhbits separase (which proteolyses cohesins allowing for sister chromatid seperation in anaphase)
Cyclin B (and D, E, and A)- halts Cdk activity

26

What are two major checkpoints that detect DNA damage?

*at Start in late G1
*G2/M phase transistion

27

What happens if DNA damage is detected?

Activates p53 (by inhibiting the normally high rate of p53 destruction)--> transcription factor that induces expression of CKIs (arrests cell cycle to allow for DNA repair)

If too much damage activates BAX to start apoptosis.

28

Steps from DNA damage in G1 to cell death....

DNA damage activates ATM/ATR kinases
ATM/ATR phos. and activate Chk1 and Chk2
Chk1 and Chk2 phos. p53 (reducing its affinity for Mdm2)
p53 is transcription factor for CKIs

29

Steps from DNA damage at G2/M phase

DNA damage activates ATM/ATR kinases
ATM/ATP phos/activate Chck1/2
Chck1/2 phos/inactivates Cdc25 which stops activation of M-Cdk

30

Bub1 activity

Bub1 kinase present in kinetochores, active in ABSCENCE of attached microtubules.

Active Bub1 inhibits initiation of cohesin proteolysis thus inhibiting anaphase

31

What are oncogenes?

mutated genes whose presence can stimulate the developement of cancer (gas pedals) Gain of function, only need mutation in one allele

32

What are tumor suppressor genes?

normal genes whose absence can lead to cancer (breaks) need mutations in both alleles. loss of function

33

What are the different types of cell death pathways? Define functions, which one is associated with inflammation?

Apoptosis- highly regulated, programmed cell death
Necrosis- largely unregulated, cells "blow up" and is associated with inflamation
Autophagy-highly regulated, actually a survival pathway

34

What morphological features characterize apoptosis and autophagy?

condensation of chromatin within the nucleus
Blebbing of plasma membrane
Cell shrinking, becomes fragmented
Phosphatidylserines are flipped to the outer layer with constitutes a signal to marcophages that the cell is dying and should be eaten.

35

Extrinsic Pathway of apoptosis

*involves signaling molecules and membrane receptors*
-ligand binds receptor, receptor trimerizes and activates adaptor proteins (FADD)
-Adaptor proteins activate procaspase 8
-Caspase 8 activates effector caspase
-triggers apoptosis

36

Intrinsic Pathway of apoptosis

*involves damage or stress which is transmitted to the mitochondria
-Mitochondria forms pore (regulated by Blc-2 family proteins) in membrane and releases cytochrome C
-Cyto C assoicates with Apaf1 to form apoptosome
-apoptosome binds and activates initiator caspase 9
-Caspase 9 then activates effector caspases

37

How is mitochondrial pore formation regulated?

Bcl-2 inhibits MOMP
Bax and Bak promte MOMP
Bid, Bad inhibit Bcl-2 = promote MOMP
**Bid links intrinsic and extrinsic pathways, can be activated by caspases and then go and inhibit Bcl-2 to allow MOMP formation and apoptosis**

38

Define autophagy... what is its purpose?

functions to maintain intracellular homeostasis under stress, involves lysosomal degradation of cytoplasmic elements and recycle A.A. and energy.
Its purpose is to prolong cell survival in the face of starvation and other stress signals.

39

mTOR

"master regulator" can promote cell survival or growth.
-Active AKT phosphorylates mTOR which then inhibits autophagy
-low energy levels/DNA damage activate AMPK, inhibits MTOR, blocks mTORs inhibition of autophagy so then you get autophagy

-AMPK can also activate CKIs

40

Beclin-1

helps initiate the autophagosome
-activated by kinase
-inhibited by Bcl-2

41

Reverse Warburg Effect

-Tumors have preferential utilization of glucose
-Signals from growing tumor cells are transmitted to neightboring cells, inducing the cells to carry out autophagy.
-These cells release lactate and pyruvate which are taken up and used by cancer cells.
-Bcl-2 inhibits autophagy, and suppresses apoptosis by preventing the formation of MOMP (can function as a oncogene)

42

What are the two ways genetic diversity is generated in meiosis?

Crossing over
random assortment

43

Why is prophase 1 unique?

replicated members of chromosome paris find each other and physically bind through synapsis (allows for crossing over between homologous chromosomes)

44

What is the synaptonemal complex?

protein based assembly that aligns the homologous chromosomes along their length

45

Define nondisjunction

errors in chromosome segregation during meiosis gives rise to daughter cells with an abnormal number of chromosomes.
Can occur during meiosis 1, meiosis 2 or mitosis

46

What are the two significant differences in the stages of mitosis and meiosis?

-there are two rounds of division in meiosis ( a single round of S is followed by two rounds of M-phase. S phase precedes prophase I, but another S phase does NOT occur between telophase I and prophase II)
-how the chromosomes are organized in the first mitotic division: homologous chromosomes (which have been repicated in S phase) pair up to form a structure composed of four daughter chromosomes called a bivalent.

47

Two effects of pairing homologous chromosomes in prophase 1

-it allows for homologous recombination
-results in the inheritance of only one duplicated member of each homologous pair of chromosomes by a daughter cell