Cell Cycle, Division, and Replication Flashcards
what is the basic function of the cell cycle?
to duplicate the DNA in the chromosomes
segregate the DNA into genetically identical daughter cells
what does each genetically identical daughter cell receive?
a complete copy of the entire genome
what are the three general parts of the cell cycle?
- cell growth and chromosome duplication
- chromosome segregation
- cell division
what does the duration of the cell cycle depend on?
- the availability of energy sources
- the way the cell is differentiated
- its surroundings
- whether the cell passed the internal tests for readiness to divide (checkpoints)
what happens during cell division of frog embryos?
embryos divide in synchrony even though they aren’t connected
what are the four phases of the eukaryotic cell cycle?
M phase (mitosis/cytokinesis)
G1 phase (growth)
S phase (synthesis)
G2 phase (checks completion)
what is M phase of the cell cycle?
consists of mitosis (nuclear division) and cytokinesis (cytoplasmic division)
the most intense, dynamic phase of the cell cycle
what is the G1 phase of the cell cycle?
growth phase
cells recover and repair
what occurs during the S phase of the cell cycle?
synthesis
duplication of genome through DNA replication
what occurs during the G2 phase of the cell cycle?
checks completion of divided cells
full replication of chromosomes
which phase of the cell cycle is the most important?
G1 phase
which phase of the cell cycle is the most tightly controlled and demanding?
S phase
when does S phase occur?
between the gap phases (G1 and G2)
what is interphase?
a combination of G1, S, and G2 phase (the entire cell cycle minus M phase)
which phase of the cell cycle is the shortest?
M phase
why is M phase the shortest?
because the cell tends to minimize the time it spends with completely inactive (condensed) genome without the ability to transcribe it
how are chromosomes represented before replication?
each chromosome has a homologous pair (each chromosome has 2 homologous chromosomes)
diploid
2n
what does n represent in chromosome karyotype?
the number of homologous chromosomes
what happens to chromosomes in each cell after S phase?
they become tetraploid (4n)
which phase is the most crucial decision-making point in the cell cycle?
G phase
which phase of the cell cycle is the longest?
G1 phase
what is the duration of cell cycle stages proportional to?
the amount of cells at certain stage in unsynchronized population
what is the order of cell cycle phases by their duration from longest to shortest?
G1, G2, S, M
where would S phase or M phase be located in the following graph?
in the dip between A and B
what kind of cells would be found at site A on the graph?
diploid
what kind of cells would be found at site B on the graph?
Tetraploid
what phase are the majority of cells found in?
G1 phase
where were the genes responsible for the cell cycle control first discovered?
in yeast
what role does cyclin and cyclin-dependent protein kinases (Cdks) play in the cell cycle control system?
they appear and disappear in a cyclic manner
Cdks play a major role in moving cells between stages
cyclin needs the Cdks to activate it
what happens to M cyclin concentration during the cell cycle?
it goes up and down depending on the stage but is always present
how was the cell cycle control system in mammals deciphered?
using frog eggs as a model system
what were the results of the experiment using the frog egg model system to decipher the cell cycle control system?
extracts taken from the frog egg at different stages can trigger or stop normal cell cycle add in trans
what happened to the frog egg when cytoplasm from M-phase was injected into the cell?
spindle easily detected
oocyte was driven into M phase
what happened when cytoplasm from interphase was injected into the frog egg cell?
blocks cell division
oocyte does not enter M phase
what does each phase have to help it through the cycle?
each phase has its own specific cyclin and Cdk (cyclin-Cdk protein complex) that regulate a different set of target proteins
when does the S cyclin begin to rise?
from the middle of G1 phase through S phase to end of G2
when does M cyclin begin to rise/end?
rises in middle of G2 phase to end of M phase
why are cyclins and Cdks important?
Cyclins drive the events of the cell cycle by partnering with a family of enzymes called the cyclin-dependent kinases (Cdks)
what heavily influences the formation of cyclin-Cdk complexes?
environmental conditions
extracellular signals that permit cells to divide.
what triggers the degradation of the previous Cdk?
transition to the next stage
what causes the destruction of cyclins?
proteasomal pathways
ubiquitylation
what does the destruction of cyclins do?
drives transition from one phase to the next
what does the Anaphase-promoting complex (APC) do?
marks M-cyclin for degradation and takes the cell out of mitosis
destroys securin and triggers segregation during anaphase
how is a cyclin degraded?
a ubiquitin chain attaches to the cyclin, separating it from the active Cdk.
This causes the cyclin to degrade and the Cdk to become inactive
how do inhibitory kinases work? What is happening in the following pathway?
Cdks protein concentrations in the cells increase gradually.
Cdk comes in inactive, phosphorylated form to trigger the abrupt activation of Cdk activity.
In this case, M-cyclin is phosphorylated by inhibitory kinase Wee1.
The removal of phosphate by phosphatase Cdc 25 activates the complex.
what happens to M-Cdk while it is phosphorylated?
it is inactive
how is M-Cdk activated?
when phosphatase Cdc 25 removes the inhibitory phosphates from it
what is the purpose of inhibitory subunits?
The activity of the complex can be transiently delayed (paused) allowing the cells to make a decision whether or not to move to the next phase, for example, from G1 to S.
how do inhibitory subunits delay the activity of a cyclin-Cdk complex?
an inhibitory subunit, like p27, binds to the active cyclin-Cdk complex, inactivating it
how does a cell exit each stage of the cell cycle?
cell only exits a phase if everything is set up properly
what happens if a cell has errors?
it gets frozen in M phase until everything is corrected
if corrections cannot be made/fixed apoptosis occurs
what happens if DNA replication is incomplete or DNA is damaged during transition from G2 phase to M phase?
inhibition of activating phosphatase cdc25 blocks entry of cell to Mitosis
what happens if chromosomes are not properly attached to spindles at the end of M phase?
inhibition of APC/C activation delays exit from mitosis
nondisjunction
what happens if the environment is not favorable during transition from G1 phase to S phase?
Cdk inhibitors block entry of cell to S phase
why is G1 phase the most important decision making point in the cell cycle?
Staying G1 in phase allows the cell to monitor the environment for stimulatory factors and to make a decision whether to proceed to S phase, or to pause, or to enter which could be permanent (either senescent or terminally differentiated-neuronal or aging cells) or temporary non-dividing (quiescent- hepatocytes) state (called G0)
what happens if you remove senescent/terminally differentiated cells? how was this determined?
you will live longer
studied in mice
what triggers cell division in mammals?
external protein activators called mitogens
what would happen if a cell is deprived of mitogens?
the cell would remain in G1 phase
what are mitogens?
they are transcription regulators that trigger cell division
what do many transcription regulators also act as?
tumor suppressors
why are transcription regulators able to function as tumor suppressors as well?
they are absent in various tumors
tumor cells tend to divide uncontrollably and devoid of those factors through the selection process.
what is occuring in the following pathway?
Activated G1 Cdk and G1/S complex phosphorylates RB protein and inactivates it and allows for cell to continue to S phase and transcribe
what is p53?
a major tumor suppressor protein that helps cells sense the DNA damage and temporarily halt the cell cycle at G1 until the DNA repair system is engaged
what happens if the cell is unable to repair DNA?
it triggers p53-dependent apoptosis
when is p53 stable?
p53 is stable once it is phosphorylated
what happens to p53 in the absence of DNA damage?
it is degraded in proteasomes
what happens when DNA is damaged?
protein kinases phosphorylate p53
p53 is stabilized and activated
active p53 binds to regulatory region of p21 gene
p21 gene is transcribed and translated
p21 Cdk inhibitor protein binds and inactivates G1/S-Cdk and S-Cdk complex
what controls S phase?
S-Cdk complex
what does the S-Cdk complex do during S phase?
it initiates replication and blocks the repetition of replication
what is necessary for the prereplication complex to initiate replication at ORI?
it must be activated by S-Cdk
what does S-Cdk do to helicase?
S-Cdk phosphorylates helicase and triggers the assembly of functional replisome
what happens if replication is incomplete at the end of S phase?
the cell can be halted at G2 phase
what does the presence of active replication during S phase do?
it prevents Cdc25 from activation, which is necessary to dephosphorylate and thus inactivating M-Cdk
what is the prereplication complex (preRC)?
the complex made up of DNA helicase and the ORC that initiates replication at the ORI
it holds together until it is phosphorylated by the S-Cdk complex
what happens to Cdks at the beginning of G1?
they are all inhibited
how are all Cdks inhibited at the beginning of G1?
While anaphase-promoting complex (APC) marks M-cyclin for degradation, it is also activated by M-Cdk at the same time.
The lack of activator and the gene expression depletes the cell from eventually all Cdks completely at the end of mitosis.
what causes the rise of Cdks?
rise of Cdks starts during G1 with accumulation of G1 cyclins that triggers the transition to S phase
how does the S-Cdk complex control S phase?
- it phosphorylates the prereplication complex, initiating replication
- it phosphorylates helicase, triggering the assembly of functional replisome
it blocks the repetition of replication
what does M-Cdk do in regards to mitosis?
it drives entry into M phase and Mitosis
how does M-Cdk work?
activated M-Cdk self-regulate (amplifies) its own activity by activating Cdc25 (positive feedback) and shutting down Wee1
what are the stages of M phase (mitosis)?
- Prophase
- Prometaphase
- metaphase
- mitosis
- anaphase
- telophase
- cytokinesis
what are the stages of interphase?
- G1
- S
- G2
what happens during interphase?
- centrosomes are duplicated
- tubulins and other proteins are synthesized
- DNA is replicated but is still in decondensed state
- Before replication, each chromosome is diploid (has a homologous pair)
- after S phase, each cell becomes tetraploid
what is the result of mitosis in most eukaryotes?
2n ⇢ 4n ⇢ 2n+2n
what is the result of mitosis in some eukaryotes, like haploid yeast)?
n ⇢ 2n ⇢ n+n
what is the result of mitosis in some eukaryotes like plants?
2Xn ⇢4Xn ⇢ 2Xn + 2Xn
what is the result of binary division (prokaryotes)?
n ⇢ 2n ⇢ n + n