cell biology- chapter 18

why do cells need to have various checkpoints and ways to control the cell cycle?

to ensure accurate DNA replication and division, preventing errors that could lead to diseases like cancer

what are the 3 main questions that you need to answer as a cell when you go through the cell cycle?

1. how am I going to divide everything inside me?

2. how do I separate each copy on each side of the cell?

3. how am I going to control these 2 processes?

when cells divide, what do they have to do first?

increase in size

what is an exception to the increase in size that cells undergo before they divide?

the embryonic frog and its cleavage stages, where the cells divide rapidly without increasing in size. this means the daughter cells are reduced in size with every division

what if the cells were not increasing in size first prior to dividing?

with every division, the size of the cell would decrease and they would end up being miniature cells

is the time it takes for all cells to divide the same?

no the time of the cell cycle differs depending on the type of cell

how many phases does the eukaryotic cell cycle include?

four phases

what are the 4 phases of the eukaryotic cell cycle?

• G1 (gap 1)

• S (synthesis)

• G2 (gap 2)

• M (mitosis)

what happens in the G1 phase?

the cell grows and prepares for DNA replication. This phase focuses on synthesizing proteins and organelles necessary for DNA synthesis

what happens in the S phase?

DNA is replicated, producing two identical copies of each chromosome

what happens in the G2 phase?

the cell prepares to enter mitosis by ensuring that DNA has been replicated correctly and by synthesizing proteins needed for cell division

what happens in the M phase?

the cell undergoes mitosis and cytokinesis

what are the 2 processes that occur in the M phase?

mitosis and cytokinesis

the most dramatic phase of the cell cycle

the M phase

what are the G1 phase, S phase, and G2 phases known as?

interphase phases of the cell cycle

what is the cell cycle controlling system in place?

a series of checkpoints and regulatory proteins that ensure the proper progression of the cell cycle

how do we prevent malignancies?

you need a tight regulation of the cell cycle

what do cancers genetically affect?

the mechanisms that control the cell cycle and inhibit the cell cycle

what are the 3 checkpoints that control the cell cycle?

• G1

• G2

• M

where is the first checkpoint located?

at the G1 phase, where the cell asks if the environmental conditions are favorable to continue the cell cycle. it ensures the cell is ready for DNA synthesis

where is the 2nd important checkpoint located?

at the G2 phase, where the cell assesses if DNA replication has been accurately completed and repairs any damage before mitosis

before anaphase, what does the cell has to make sure?

all chromosomes are properly attached along the mitotic spindle

where is the 3rd important checkpoint located?

at the M phase 9anaphase), where the cell checks for proper alignment of chromosomes on the mitotic spindle before proceeding with cell division

what is one universal characteristic of the cell cycle among all eukaryotes?

it is highly conserved and similar in all eukaryotes

why is it special that the mechanism of the cell cycle is shared among eukaryotes?

it allows scientists to use different eukaryotic cells to study the cell cycle with little variation and be able to draw important conclusions concerning the research of cell cycle control

what does the cell-cycle control system depend on?

cyclically activated protein kinases that get activated and deactivated, known as CDKs

what does the C in CDK stand for?

cyclin, which is a protein that need to bind on the enzyme in order to activate it

what are CDK, referred to as cyclic?

because their levels are circulating

in order to activate a CDK, what 2 things need to happen?

• needs to bind a cyclin

• CDK needs to be dephosphorylated

how does CDK get activated?

if it becomes dephosphprylated

what does a CDK have in its inactive state?

phosphate groups that cause inhibition

how can CDK/cyclin complexes control different steps and checkpoints in the cell cycle

depending on the combination of CDK and cyclin that come together

what cyclin can you find at the end of G1?

• S cyclin

• G1/S cyclin

what does the S cyclin bind to and form?

a CDK, forming an S-Cdk complex

what does an S-Cdk complex do?

pushes the cell cycle from the G1 to the S phase

what does the G1/S cyclin do?

bind to a CDK, forming a G1/S-Cdk that pushes the cell from the G1 to the S phase

what cyclin can you find at the end of the G2 phase?

• M cyclin

• G2/M cyclin

what does the M cyclin bind to and form?

Cdk, forming an M-Cdk complex

what does the M-Cdk complex do?

pushes the cell cycle from the G2 phase to enter mitosis

what are cyclin concentrations regulated by?

gene transcription bringing the levels up and proteolysis (breakdown of proteins) bringing cyclin concentration down

what happens to the levels of cyclin through the cell cycle?

it goes up and down

how do cyclin levels increase?

the genes that express the cyclin increases

how do cyclin levels decrease?

cyclin specific proteases degrade the cyclins, bringing their concentration down

what is one way that the degradation of cyclins take place?

through ubiquitination

how do you destine proteins for the proteosome?

add ubiquitin molecules on them

what is the anaphase promoting complex?

it adds multiple ubiquitin molecules creating a ubiquitin chain on the active cyclin-cdk complex to target it for degradation

what happens to the cyclin once it has ubiquitin on it?

it is marked for degradation by the proteasome, leading to its destruction and the regulation of the cell cycle

what happens when you over ubiquitinate a protein?

youre creating a flag, sending it to the proteosome in the cytoplasm that breaks down proteins

what does the mitotic CDK attach to?

M cyclin

what else attaches to the mitotic CDK along with the M cyclin?

a phosphate group that was added by an inhibitory kinase ( Wee1)

what dephosphorylates the inactive M-Cdk?

the activating phosphatase (Cdc25)

what can active Cdks go do after they have been dephosphorylated?

start phosphorylating other proteins that are important for the cell cycle and push the cell cycle along

what can Cdk activity be blocked by?

other proteins that are inhibitory for the Cdk

what is an example of an inhibitory protein that blocks the Cdk activity?

p27

if cyclins were never expressed, and we didnt have any what would happen?

that would be a problem for the cell cycle because cyclins are essential for activating Cdks, leading to cell cycle progression

if the phosphatases or kinases that phosphorylate/dephosphorylate the CDKs were regulated, what would happen?

regulating these proteins would disrupt the activation and inactivation of Cdks, potentially halting cell cycle progression.

what can block entry to the S phase?

proteins such as p27 can inhibit Cdks blocking entry to the S phase and preventing DNA replication and cell cycle progression

if you inhibit the activating phosphatase (Cdc 25) what happens?

the Cdk would not get activated/phosphorylated, blocking the cell cycle progression at G2 and block entry into mitosis

if you go into mitosis and are dealing with the active M-Cdk complex, but inhibit APC, what happens?

ubiquitin wont add to the cyclin on the M-Cdk complex, causing cyclins to accumulate and preventing exit from mitosis

what is created at the end of mitosis if APC doesnt work?

a bottleneck occurs where the cyclins accumulate, leading to prolonged mitosis and potential cell cycle arrest

what are some things a cell could do at the G1 checkpoint?

• a cell could either proceed to DNA synthesis in S phase

• enter a quiescent state (G0) if it receives unfavorable conditions or signals

• initiate apoptosis if it detects irreparable damage or stress

• undergo terminal differentiation if it has reached its specific cell type or function

what is G0?

where cell remain idol for things to be fixed. It is a quiescent state where cells are metabolically active but not actively dividing, often entering this phase in response to unfavorable conditions.

what happens at the G1 checkpoint if the cells sense that certain things are not okay and things need to be addressed?

the cell will stay in the G1 phase for a while

what happens if the cell needs even more time to fix things after it’s already been held in the G1 phase?

it’ll go into the G0 phase

what does it mean for a cell to become permanently differentiated?

it stops dividing and has to change and get a certain structure to conduct a certain type of function (nerve cell or muscle cell)

in what phase are CDKs stably inactivated?

G1

when the cell is in the G1 phase what can it not go in without?

being certain that the DNA has no errors and everything else is suitable for replication

what happens in G1 phase once the cell is suited for replication?

what does it mean for a cell to proliferate?

to get the cell cycle going at high speeds

what is one thing that really pushes cells to proliferate?

mitogens

what are mitogens?

outside molecules/chemicals that when they bind to receptors on cells, they result in the speed up of the cell cycle

what is an example of a mitogen?

LPS (lipopolysaccharide)

what type of cell does LPS bind to?

B cells

what happens when LPS bind to LPS receptors on B cells?

the B cells nonspecifically proliferate

what other type of cells can mitogens activate?

• T cells

• macrophages

• white blood cells

if you were to look in the nucleus, how many proteins are there that occupy the promoter region of certain cyclins?

7

what do the proteins that occupy the promoter region of certain cyclins do?

silence the expression of the cyclins or the CDKs

what happens if the expression of the cyclins or CDKs is silenced?

the cell will stay at the phase it is at

what is a protein that has been implicated in the silencing of the expression of the CDKs?

the Rb protein (retinoblastoid protein)

what does the Rb protein do?

bind to promoter regions and silence CDKs from being expressed so you don’t proceed in the cell cycle

what happens if a mitogen bind to a receptor at the top of the cell?

it phosphorylates the inhibitory proteins like the Rb protein, inactivating them, causing conformational change and the inhibitory protein detaches from the promoter region

what happens when the inhibitory protein detaches from the promoter region?

it allows the initiation of the transcription of the CDK genes to make CDKs

what happens when the transcription of CDK genes is initiated?

mRNA is produced, which is then translated into a CDK protein enzyme, which will then bind a cyclin and be able to push the cell into the next phase of the cell cycle

what is the Rb protein/ gene frequently seen in?

cancers

what happens if the Rb gene that encodes the Rb protein is faulty/mutated/missing?

then you are missing a major inhibitory protein meaning there is nothing to stop cyclins and CDKs from constantly binding, coming together, being activated, and pushing the cell cycle forward

how is the Rb protein involved with cancer?

in cancer you have uncontrolled and non stop cell proliferation. this means the gene that encodes the Rb protein is either missing or mutated

what can temporarily halt progression through G1?

DNA damage

if the cell is in the G1 phase about to enter the S phase, but the DNA is not properly in place and damaged then what happens to the cell?

it doesn’t proceed and stays at the G1 phase temporarily until it is fixed

damaged DNA leads to what?

the phosphorylation and activation of a protein known as p53

what happens when the protein p53 gets phosphorylated?

it binds to a promoter region of the p21 gene, starting the transcription of p21

what happens when the activated and phosphorylated p53 genes binds to the promoter region of the p21 gene?

mRNA is produced which eventually gets translated into the p21 protein

what is the p21 protein?

a G1/S CDK and S CDK inhibitor

what happens to the p21 gene if the DNA damage is so bad?

the p21 gene if it’s overly expressed, turns pro-apoptotic and drives apoptosis and kills the cell completely

what can cell do to delay division for prolonged periods?

enter specialized nondividing states

what are two things that the cell needs to worry about during the S phase?

1. you need to initiate replication and have each chromosome make a copy

2. You need to make sure the chromosomes make only one copy

what needs to happen after a chromosome replicate itself?

re-replication needs to be blocked

what comes into play in order to block re-replication?

the S-Cdk cyclin

what is the S-Cdk responsible for?

to start the DNA replication but also block subsequent replication cycle of the chromosomes

when DNA replicates, what does it have to initiate replication?

the origin of replication

what is the origin of replication?

a few nucleotides that designate when where the DNA replication is going to start