Cell Cycle Control & Cell Division Part II (Exam IV) Flashcards
Passage through the start checkpoint in late G1 launches DNA replication & the ______ of the cell cycle
S-Phase
DNA replication occurs at specific sites:
Origins of replication
The initiation phase of DNA replication is divided into two steps:
1- late mitosis-early G1
2- Onset of S phase
In the first initiation step of DNA replication in late mitosis-early G1 ______ assembles at the origins of replication
Prereplication complex
In the second step of initiation of DNA replication, in the onset of S phase is when the prereplication complex _____ the formation of the _____
Nucleates
Preinitiation complex
The prereplication complex is formed by various molecules including:
Cdc6 & Cdt1 & also a helicase
The prereplication complex occurs in:
G1
The prereplication complex forms at the:
Origins of replication
After the prereplication complex is formed, it is just waiting on:
The right signals
The signal that the phosphorylation complex is waiting on is:
S-Cyclin-Cdk
The S-cyclin-Cdk is present in the S phase of the cell cycle because of:
The G1/S-Cdk activity that precedes it
The S-Cyclin will function to phosphorylate the _____ thereby degrading it
Cdc6
After the S-cyclin has degraded the Cdc6, another set of proteins come in called the:
Preinitiation complex
The Preinitiation complex functions to:
Launch DNA replication
At the end of DNA replication is when the ______ phase starts
G2/M
The three steps of G1, S & G2/M:
- Starts with the _______
- Add _____, _____ & ______ to form the prereplication complex
- The prereplication complex is converted into a _____ by addition of proteins that bind to the DNA through the action of ______ phosphorylating other proteins present & the DNA is opened in up by the action of _____
Once DNA replication is complete, you enter the ______ checkpoint
1- origin of replication
2- Cdc6, Cdt1, helicase
3- preinitiation complex, S-Cdk, helicase
G2/M
What cell cycle phase does this process occur in:
Formation of the prereplicative complexes at all the replication origins
G1
What cell cycle phase does this process occur in:
Starts by the formation of the preinitiation complex & initiation driven by the S-Cdk
S
What cell cycle phase does this process occur in:
DNA replication occurs
S
What cell cycle phase does this process occur in:
M-Cdk comes along & that triggers chromosome separation & cytokinesis to create the daughter cells
M
What cell cycle phase does this process occur in:
Driven by the activation of APC/C complex that leads to inactivation of the Cdk
G1
What cell cycle phase does this process occur in:
Assembly of the prereplicative complexes at the origins of replication
G1
If we are talking about the G2/M checkpoint, which phase of cell-cycle is this associated with:
Mitosis
The G2/M checkpoint is responsible for insuring that:
All of the DNA has been properly replicated
What molecules activity abruptly increases at the G2/M checkpoint
M-Cdk
Abrupt increases of the M-Cdk activity at the G2-M checkpoint drives:
Entry into mitosis & early mitosis events
Responsible for inducing the assembly of the mitotic spindle, chromosome condensation, promotes breakdown of nuclear envelope, rearrangement of the actin cytoskeleton & Golgi apparatus:
M-Cdk mediated phosphorylation of specific proteins
Events triggered by M-Cdk mediated phosphorylation of specific proteins in conjunction with two other families of protein kinases (4):
1- induces assembly of mitotic spindle
2- chromosome condensation
3- promotes breakdown of nuclear envelope
4- rearrangements of the actin cytoskeleton & Golgi apparatus
How long does it take mitosis from start to finish:
1 hour
Five phases of mitosis:
Prophase
Prometaphase
Metaphase
Anaphase
Telophase
The interphase events of mitosis encompass:
G1/G0 phase
S phase
G2 phase
What phase is separate from interphase:
M phase
At prophase the replicated chromosomes consist of:
Two closely-associated sister chromatids
What phase of mitosis is this:
Intact nuclear envelope
Centrosomes forming outside the nucleus- beginning to move apart
Forming mitotic spindle
Condensing replicated chromosomes consisting of two sister chromatids
Prophase
Allows for the chromosomes to attach to spindle microtubules via their kinetochores:
Breakdown of nuclear envelope
What phase of mitosis is this:
Breakdown of nuclear envelope
Chromosomes attach to spindle microtubules via their kinetochore
Chromosomes in active motion
Prometaphase
Important for the moving apart of chromosomes:
Kinetochores
What phase of mitosis is this:
Chromosomes are aligned at the equator of the spindle
Kinetochore microtubules attach sister chromatids to opposite poles of the spindle
Metaphase
What phase of mitosis is this:
Sister chromatids synchronously separate to form two daughter chromosomes
Kinetochore microtubules shorten
Spindle poles move apart
Anaphase
What phase of mitosis is this:
Set of daughter chromosomes at the spindle pole
Set of daughter chromosomes decondense
New nuclear envelope reassembles around each set
Contractile ring starts to form
Telophase
What marks the end of mitosis:
Completing the formation of of two nuclei
During telophase, the division of the cytoplasm begins with:
Contraction of the contractile ring
Cytoplasm is divided in two by a contractile ring of actin & myosin filaments, which pinches the cell in two to create two daughters, each with one nucleus:
Cytokinesis
Separation of the two daughter cells is accomplished through:
Cytokinesis
Following cytokinesis each daughter cell will have a complete ______ surrounding all of the ____
Nuclear envelope; chromosomes
Following cytokinesis we have:
Two identical daughter cells
When fewer ribosomes are made (for example in an ESCO2 mutation) this will ultimately lead to:
Decreased protein synthesis
Prenatal growth retardation (mild to severe), craniofacial abnormalities such as microcephalic & cleft lip/palate & limb malformations due to a homozygous mutation in ESCO2:
Roberts syndrome
Roberts syndrome is due to a ______ mutation in the gene _____
Homozygous mutation; ESCO2
ESCO2 is a gene responsible for encoding a _____ important for the formation of the cohesion complex that binds to chromosomes & creates cohesion between sister chromatids
Acetyltransferase
The Acetyltransferase encoded by ESCO2 is important in the formation of the:
Cohesion complex
The cohesion complex is responsible for binding chromosomes & creating:
Cohesion between sister chromatids
Studies suggest that the ESCO2 mutation lead to decreased:
Ribosome production
The metaphase to anaphase transition involves:
Proteolysis
During proteolysis:
The APC/C protein binds to ____ to produce an active APC/C molecule
This process is regulated by:
The active M-Cdk complex ubiquitylates & degrades a protein called:
Securin is normally bound to an inactive protein called:
When securin is ubiquinated & subsequently degrades the separase becomes _____
Cdc20
M-Cdk
Securin
Separase
Active
Molecule responsible for breaking down the cohesion complexes that hold the sister chromatids together:
Activated separase
The breakdown of the cohesion complexes by activated separase occurs during:
Anaphase
Three types of basic signals that control cell division:
Mitogens, growth factors, survival factors
Stimulate cell division mainly by stimulating G1/S-Cdk activity that inhibits intracellular negative controls that block the progression through the cell-cycle
Mitogens
Stimulate cell growth (increase cell mass) by stimulating protein synthesis & inhibiting protein degradation:
Growth factors
Suppress programmed cell death (apoptosis)
Survival factors
Mitogens generally act through a highly generalized:
Cascade of mitogen-activated protein kinases (MAPK)
In the MAPK cascade:
The initiate stimulus stimulates a ______
MAPKKK
In the MAPK cascade:
The stimulation of the MAPKKK will lead to the simulation of _____ which leads to the stimulation of _______ & ultimately leading to ____
Stimulus —> MAPKKK —> MAPKK —> MAPK —> biological response
When mitogens bind to their cell surface receptor they will trigger:
Multiple intracellular signaling pathways
A major pathway that the mitogen trigger is the:
Small GTPase Ras signaling proteins
The Ras protein leads to the activation of a:
MAP-Kinase cascade
When the Ras leads to the activation of a MAP-kinase cascade that leads to the activation of:
Multiple early gene expression
Genes that are turned on very early or almost immediately after a mitogen binds to its receptor
Immediate early gene expression
One of the immediate early gene expressions is in a gene called:
Myc
Myc is thought to promote cell cycle entry by:
Increasing the expression of genes encoding the G1 cyclins
Results in increased G1-Cdk activity:
Myc increasing the expression of genes encoding G1 cyclins
One of the key functions of G1-Cdk is to activate the:
E2F proteins
The E2F proteins are:
Gene regulatory factors
Normally the E2F proteins are inhibited by an interaction between E2F & the:
Retinoblastoma protein family (Rb)
What is responsible for phosphorylating the Rb protein:
G1-Cdk
When the Rb protein is phosphorylated y G1-Cdk, this (3):
1- renders it inactive
2- reduces it binding to EF2
3- Frees EF2 to activate expression of its target genes
When the EF2 is free it:
Activates the expression of target genes
One of the immediate downstream targets of activated E2F is:
S-cyclin
When activated the E2F proteins leads to:
S-phase of gene transcription
Can directly lead to cell growth:
Growth factor & extracellular factor
Can directly lead to to cell division:
Mitogens & extracellular factor
Causes cell growth to go into cell division:
Extracellular factor
Summary of mitogen induced cell-cycle entry & S-phase initiation:
1- mitogen binds to its receptor leading to the activation of ____
2- the activation of RAS leads to the activation of ____
3- the activation of MAPK leads to a _____
4- the transcription factor binds to ______
5- the immediate early genes leads to _______
6- myc expression leads to the activation of _____
7- eventually you get DNA synthesis through early inhibition of ____
1- RAS
2- MAPK
3- transcription factor
4- immediate early genes
5- Myc expression
6- G1-Cdk
7- Rb protein
Signals through PI3 kinase/AKT signaling
EGF
EGF works through what three pathways:
1- ERK
2- JAK/STAT
3- PI3 Kinase/AKT
EGF pathway that leads to increased protein synthesis:
PI3/AKT
EGF pathway that leads to cell survival & protein synthesis:
ERK
EGF pathway that leads to cell survival:
JAK/STAT
Growth factor that has an affect on cell cycle progression
TGF-Beta
When TGF-beta binds to the type I & type II receptor complex, that leads to the:
SMAD pathway
Proteins targeted by the SMAD pathway
P15
P21
P15 & P21 proteins (that are targeted by SMAD) result in the inhibition of:
Cyclin E
Cyclin D
Occuring at the same time of SMAD activating P21 & P15, there is a second pathway that leads to the inhibition of:
Cdc25
Growth factors are ultimately shutting down the cell cycle process in favor of:
Growth
When growth factors bind to their receptors this leads to:
A series of intracellular events
The signaling events resulting from growth factors binding to their receptors in many instances involve the:
PI3 kinase
The PI3 kinase leads to the intracellular signaling molecule:
PIP3
Downstream, PIP3 leads to the activation of the:
TOR pathway
The TOR pathway eventually leads to:
Protein synthesis & growth
