Cell Cycle

Question 1

What are the stages of the cell cycle? briefly summarize their functions

Answer 1

G1: has a checkpoint (checks whether replication can occur), perpares for DNA replication, monitoring DNA integrity and checking environmental conditions
S: Synthesis, DNA replication to form sister chromatids
G2: has a checkpoint (checks if cells can divide), prepares for mitosis, checking for DNA damage and accurate replication
M: Prophase, interphase, metaphase, anaphase, cytokinesis (cell division by condensing chromosomes, aligning at metaphase plate, pulling them apart, forming nuclear envelopes, dividing in half)

Question 2

what are some ontrol mechanisms used in the cell cycle?

Answer 2

regulatory proteins and biochemicals switches govern progression, check DNA replication, mitosis, chromosome segregation

Cdks: type of protein (cyclin-dependent kinases) which form molecular switches to control critical events

Question 3

types of cyclins, their roles and regulation

Answer 3

G1/S cyclins: activate cdks to move cell into DNA replication
S cyclins: binds Cdks during S phase for replication
M cyclins: promote mitosis
G1 cyclins: allow passage through restriction point in late g1

regulation: activated by binding to cyclins, inhibited by inhibitory proteins, ubiquitin-mediated degradation (SCF and APC ubiquitin ligases target cyclins for degradation to control levels and ensure proper cell cycle progression

Question 4

name the 3 cell cycle checkpoints, explain their functions and how they work

Answer 4

1. dna replication checkpoint: monitors for unreplicated DNA by temporarily blocking M-Cdk activation
2. spindle attachment checkpoint: ensures all kinetochores are attached to the spindle before proceeding to anaphase
3. dna damage checkpoint: regulates cell cycle progression in response to DNA damage, p53 prevents entry into S-phase if DNA is damaged

Question 5

explain total cell mass

Answer 5

cell division and cell death balance out to determine the total cell number and mass, with cell growth influencing the size of organs and organisms, it is also dependent on extracellular factors

Question 6

explain extracellular factors that affect total cell mass and regulation

Answer 6

• growth factors: increase protein synthesis and decrease protein degredation, essential for cell growth
• mitogens: increase cell division by promoting entry into S phase from G1
• survival factors: decrease apoptosis, crucial for cell survival

Question 7

how do growth factors affect receptor activation?

Answer 7

GFs act through receptor tyrosine kinases (RTKs) which have intrinsic enzyme activity

• ligands bind to RTK leading to receptor dimerization and autophosphorylation, initiating intracellular pathways and phosphorylating ribosomal protein S6 to increase translation of vital proteins, promote cell growth and survival

Question 8

how do miotgens control the cell cycle

Answer 8

mitogens (extracellular signals) stimulate cell proliferation, cyclin synthesis and Cdk activation, promoting enrty into S-phase
- mitogen signal –> reenters G1 and cell cycle continues, otherwise cell cycle enter G0 (restriction point and attepts to fix issue)
- mitogen binds to its receptor and activates Ras while inactivating Rb proteins, and subsequently the MAP kinase pathway, leading to increased production of cyclins and progression into S phase

Question 9

how do survival factors influence apoptosis?

Answer 9

survival factors are required to prevent apoptosis and act via protein kinase B to inhibit apoptotic pathways, Bcl2 family proteins regulate cell survival by controlling cytochrome c release and inhibit apoptosis through the activation of PKB phosphorylates

Question 10

explain abnormal mitogenic stimulation and prevention

Answer 10

mutations lead to unregulated cell proliferation and inappropriate entry into S-phase due, lack of p53 degredation to excessive Ras or Myc (may be cancerous), regular cells can detect and prevent further division,

Question 11

what is apoptosis?

Answer 11

programmed cell death, regulates number of cells, non-traumatic and cytotoxic

Question 12

list the characteristics of programmed cell death

Answer 12

intuition, significant structural changes, orderly disposal, cell-death mutants

Question 13

explain initiation in apoptosis

Answer 13

triggered by internal and external signals that activate a cascade of proteins promoting cell death

Question 14

explain the significant structural changes that occur in apoptosis

Answer 14

involves significant biochemical and morphological changes in cell, including chromatin condensation, cytoplasmic shrinkage, nuclear fragmentation, DNA laddering, blebbing, eventual cell fragmentation

Question 15

explain the orderly disposal that occurs in apoptosis

Answer 15

cell marked for phagocytosis by a macropase through exposure of phosphatidylserine on cell surface

Question 16

explain the cell death mutants in apoptosis

Answer 16

certain genes are crucial for apoptotic process, leading to discovery of capsases

Question 17

what are capsases? explain the function

Answer 17

essential enzymes that cleave cellular proteins and contribute to changes observed in cell death, they directly cut proteins or cause a self-amplifying cascade

Question 18

name the two major apoptotic pathways, describe them

Answer 18

extrinsic: triggered by external signals that activate death receptors leading to caspase activation and apoptotic cascade

intrinsic: triggered by internal signals like dna damage and loss of survival factors (example: Bcl-2 family protein like Bax and Bak, releases from mitochondria, leading to the formation of an apoptosome and activation of caspase cascade)

Question 19

how does apoptosis work for development and maintenance

Answer 19

nerve growth factor acts as both a growth and survival factor, influencing the apoptotic pathway, mutations affect apoptotic proteins that lead to developmental abnormalities and excessive cell division

Question 20

list the major events of mitosis

Answer 20

• centrosome duplication in G2
• mitotic spindle formation in prophase
• chromsome condensation in prophase
• nuclear envelope breakdown in prometaphase
• chromsome attachement to MT starts in prometaphase
• metaphase plate
• anaphase

Question 21

what do increased dynamic changes in MTs lead to?

Answer 21

dynamic changes are controlled by m cdk, which decreases MAP activity, reduces MT stability, and increases kinesin activity

Question 22

list the components of the mitotic spindle and their functions

Answer 22

microtubules (astral, kinteochore, overlap), motor proteins (kinesin-related +, dynein -), chromsomes (chromatids), centrosome (centrioles, PCM)

Question 23

how do motor proteins affect spindle assembly?

Answer 23

• motor proteins cross-link antiparallel MTs
• • end-directed kinesin-related proteins (like KRPs) which self-associate with each other with each other’s tail domains
• they slide and overlap MTs past each other to promote elongation of the mitotic spindle
• some motor proteins cross link adjacent MTs with multimeric - end dyneins ad kinesin-14 arranged towards the minus end, creating a foci at poles

Question 24

how are spindle poles separated?

Answer 24

prophase, KRPs push and overlap MTs while dyneins pull astral MTs

Question 25

how are chromsomes condensed and when

Answer 25

during prophase, cohesin and condensin bind ATP and DNA, they cross-link, and cohesin is replaced by condensin, chromosomes are condensed with energy from ATP hydrolysis and phosphorylation of condensin by M-Cdk

Question 26

how are kinetochores attached

Answer 26

during prometaphase, astral MTs catch kinetochores to increase MT stability, astral MTs become kintochore MTs with bipolar attachment and balance by astral ejection force, + end is attached to the kinetochore in metaphase where the metaphase plate is formed, motor proteins on both poles provide chrosomose stability along spindle

Question 27

what motor proteins are involved in kinetochore attachment

Answer 27

KRP (depolymerase), CENP-E (stabilizes), Dynein (moves towards minus)

Question 28

what happens if motor proteins are missing

Answer 28

chromsomes become trapped near poles and kinesin proteins are lacking

Question 29

explain poleward flux

Answer 29

movement of tubulin subunits from + end of MT toward spindle poles of mitosis, helps maintain dynamic instability of MTs and ensures proper cchromosome alignment with segregation contributing to depolymerization at spindle poles

Question 30

balance at the metaphase plate is maintained by

Answer 30

motor proteins and poleward flux

Question 31

explain anaphase a separation

Answer 31

poleward movement of chromatids by shortening kinteochore MTs
1. MT depolymerization at + end
2. continual loss of tubulin at - end without addition at + ends

Question 32

what are the 2 separation forces

Answer 32

MT disassembly driven by chromatid movement and poleward flux at onset of anaphase

Question 33

explain the combined model for anaphase a

Answer 33

kinesin 13 depolymerizes at both ends, creating a dam 1 ring around MT to maintain attachment between MT and chromatids, depolymerization powers movement as it happens more rapidly at the +

Question 34

explain anaphase b separation

Answer 34

pulling by motor proteins at poles, pushing by motor proteins at mitotic spindle to further elongate it
- KRPs cross-link and push overlap MTs apart
- dyneins anchored to cell cortex pull themselves toward - end of astral MTs