Cell Cycle Flashcards
What is the amount of time it takes for yeast cells and mammalian intestinal cells to replicate?
Yeast: 1.5-3 hours
Intestinal cells: 12 hours
Does overlapping occur in the stages of cell division?
Yes! Bc cytokinesis begins before mitosis ends!
What is the longest phase in the cell lifecycle?
Interphase!
What 3 sub parts make up interphase?
G1 phase, S phase, and G2 phase
What happens in G1 phase?
-one copy of DNA present, the cell is making more stuff/helpers in order to get ready to replicate DNA!
What is the START check point?
The checkpoint after G1 before starting S phase
What happens in S phase?
-DNA replicates once
What happens in G2 phase?
-2 copies of DNA present, the cell is making stuff (lots of organelles and microtubules) in order to prep for division soon occurring
What is the one phase that is not a part of interphase?
M phase! (This is where division and cytokinesis occurs)
What does flow cytometry do?
It is a way to see how much DNA is in cells at any given time, proved that cells spend most of their lives in G1 phase
What phase within interphase do cells spend most of their life in?
G1 phase! (Also called G0, the non dividing state)
What are the three major chromosomal events that occur in S phase and M phase?
Replication (S phase), Segregation (M phase), Separation
What are the 3 “check points” in cellular replication?
1: START transition
2: G2/M transition
3:Metaphase to Anaphase transition
What happens if a cell gets held up at a check point?
It will be given more time to see if it can fix the problem, if not it will commit apoptosis
What happens at the G2/ M transition?
It checks that DNA was replicated correctly before Mitosis occurs
What happens at the Metaphase to Anaphase transition?
Makes sure all sister chromatids are going to opposite sides correctly before cytokinesis
What is in charge of running Cell Cycle Checkpoints?
Cyclin dependent kinases! (CDKs)
-they phosphorylated proteins that drive the cell cycle
What must occur in order for a CDK to be active?
It must be bound to cyclin!
-the presence of cyclin and its specific type are what control the work of CDKs
Are cyclins phase specific?
Yes! The phase-specific type arises in concentration following the previous phase to get CDKs ready to work
(ex: M-cyclin, S-cyclin)
What binds a CDK to a cyclin?
CDK-activating kinase (CAK)!
-activated CDK once cyclin is there by adding a phosphate to a specific binding site
What are the two ways that CDKs can be deactivated?
1: Wee 1 kinase
2: CDK inhibitor proteins (CKI) for example: p27
How does Wee 1 kinase work?
It adds inhibitory phosphate to separate site on the CDK to turn it off
-CdC25 phosphatase can remove the inhibitory phosphate to turn it back on if needed!
How do CDK inhibitor proteins (CKIs) work?
They are like a claw that physically makes it inactive if it grabs ahold
What are some stressors that would cause CDKs to not allow a cell past a checkpoint in replication?
DNA damage, unreplicated DNA, chromosomes unattached to the spindle
What are tumor suppressor genes?
“Breaks” for ex: P53
-stop cell from progressing replication if something is wrong
-p53 is the most important tissue suppressor gene, over 50% of tumors have an inactivated p53 protein
What are Oncogenes?
“Gas pedals” for ex: Ras
-drive the cell cycle forward
What is the pathway for how DNA damage stops the cell cycle?
1: DNA damage stimulates p53
2: p53 activates transcription of CKI protein (p21)
3: p21 (CDK inhibitor protein) glad grabs the CDK and stops it from working, ergo stopping the cell cycle
What would happen if p53 didn’t respond to DNA damage?
The cell would replicate damaged DNA and eventually would lead to cancer
How does radiation help cancer patients?
It causes highly specific damage to cells that should recruit p53 to stop those cells from replicating so it hopefully stops cancer from dividing
-only works if p53 is still active!
At what point in the cell cycle do cells physically grow in size?
G1 (before DNA replication-S)
G2 (before mitosis-M)
What part of DNA replication begins in the G1 phase?
The “Licensing” of Origins AKA “loading the Pre-replicative complex”
-ORC is bound to replication origin
-Cdc6 associates beginning in G1
-those two pair up to load the DNA replication helicase in an inactive form
(All ready to go as soon as S starts)
What subparts make up the Pre-replicative complex?
-ORC, Cdc6, and inactive helicase at the replication origin
What two things occur during the initiation of replication in S phase?
1.) S-CDK phosphorylates helicase activator proteins to turn on helicase
2.) DDK phosphorylates DNA helicase to turn it on
this initiates DNA replication
How is duplicate replication prevented in S phase?
S-Cdk phosphorylates ORC, Cdc6, and Cdt1 to DEACTIVATE them
-they are dephosphorylated to turn them back on at the end of mitosis, so they they don’t rep the same origin twice in one mitosis
How is Cohesion utilized during DNA replication?
Cohesion (looks like circular hair clip) is added to length of chromosome during rep to keep things organized.
-Cohesion rings encircle both sister chromatids
What does M-Cdk do?
During M phase, it: condenses replicated chromosome, induces assembly of mitotic spindle, breaks down nuclear envelope, and rearranges actin cytoskeleton
How is M-Cdk activated?
-M-Cdk levels begin building up in G2, but aren’t activated until M phase!
-M-Cdk is kept inactive by Wee1 adding an inhibitory phosphate, until Cdc25 is activated once starts M phase.
-CDC25 suppresses Wee1, and M-CDK is activated when CDC25 dephosphorylates it!
(This is positive feedback loop!)
How is the activation of M-Cdk a positive feedback loop?
Because the synthesis of M-Cdk signals for more CDC25 to be made, which makes more M-Cdk!
-also, presence of M-Cdk represses Wee1, which makes more M-Cdk!
How does M-Cdk compact DNA?
M-Cdk phosphorylates Condensin to help loop up DNA!
-condensin is 5 subunit protein that coils up DNA
What do centrosomes become during S phase?
Spindle poles! On two ends of the cell the microtubules pulling the sister chromatids apart in the middle are anchored here
What are the three types of microtubules used during mitosis?
1: Kinetochore: the ones that reach out and touch DNA
2: Astral: the ones that position the spindle poles at the back ends of the cell
3: Interpolar: connect across the two spindles and push them apart, interlap with each other
Where do microtubules attach to chromosomes?
At the Kinetochore!
-the middle of the chromosome, the center of the “X”
What orientation do kinetochores have?
bi-orientation!
-arranged back to back so they the chromatids are evenly split
What does the Ndc80 complex do?
It both anchored the microtubule to the Kinetochore and allows for Microtubule Dynamics at the plus end to keep going on (growing and shrinking) by forming ring around sides of microtubules to hold on
-growth=pushes to meta plate
-shrinking = pulls back to spindle pole
What does correct spindle tension do?
Correct spindle tension confirms that microtubules are at right place on Kinetochore and allows mitosis to proceed, it increases microtubule binding affinity
What regulates the Anaphase?
The Anaphase Promoting Complex/ Cyclosome (APC/C)
How is APC/C activated?
Cdc20 binding activates it, it then acts like an UBIQUITIN LIGASE!
-it tags M-cyclin for destruction since its job is now done (as well as S-cyclin!)
How does APC/C cause the cell to transition to Anaphase?
APC/C degrades SECURIN, which was inhibiting SEPARASE but now SEPARASE is a free protease that cleaves cohesins, and separates sister chromatids
What would happen if there was not enough tension in the Kinetochore?
It would stop the cell from going into Anaphase bc Mad2 and BubR1 would be activated and would degrade APC/C
What is nondisjunction versus proper disjunction?
Nondisjunction= incorrect separation of sister chromatids
Proper disjunction = when chromatids separate correctly
What does aneuploid mean?
The cell has an abnormal chromosome number
What often causes nondisjunction?
The spindle assembly checkpoint does not operate properly
What are two examples of nondisjunction genetic disorders?
1: Down syndrome (trisomy at chromosome 21)
2: Kleinfelter syndrome (47 trisomy/ XXY)
-males with extra X chromosome, mixed sex characteristics
What happens if a cell is stuck at a check point?
Unicellular organisms: just keep going
multicellular: commit apoptosis to protect the organism as a whole
What are the mechanics of how P53 causes P21 to stop cell cycle?
p53 is phosphorylated when DNA damage occurs, it then binds to the p21 gene and causes its transcription!
What are the two mechanisms that inhibit CDKs?
1.) Wee 1 kinase
2.) CDK inhibitors AKA CKIs (p27)
