Cell Cycle, Division and Production Flashcards
What is the function of Cell Cycle?
to duplicate accurately the amount of DNA in chromosomes, segregate the DNA and Divide cell into genetically identical daughter cells (each cell receive complete copy of entire genome).
- Cell Duplication
- DNA segregation
- Cell Division
What does the cell cycle duration depend on?
duration of cell cycle depends on factors:
1. availability of energy sources
2. the way the cell is differentiated
3 . its surroundings
4. Whether the cell passed the internal tests for readiness to divide (checkpoints).
ex: cell cycle in flies are 8 mins, mammals epithelial cells- 12 hours, frogs- 30 mins (divide synchronously) and mammal fibroblasts- 20 hours.
What are the four phases in the cell cycle? Describe them. What is interphase?
G1 phase, S phase, G2 phase and M phase.
M phase (mitosis or nuclear division)- is the most intense, dynamic phase of cell cycle (a form of cell division. Cytokinesis (cytoplasmic division) also part of M phase.
S phase- Duplication of genome that occurs between two GAP (G) phases (G1 and G2). S phase- most tightly controlled and demanding process.
Interphase– a combination of G1, S and G2 phase (the entire cell cycle minus M phase).
Which phase is the most crucial decision-making point in the cell cycle? Why is it an important decision making point in the cell?
G phase (G1 specifically) Staying in G1 phase allows cell to monitor the environment for stimulatory factors, make a decision whether to proceed to S phase, or pause, or enter which could be permanent (either SENESCENT or TERMINALLY DIFFERENTIATED) or temporary non-dividing QUIESCENT state called G0.
What is the shortest phase of the cell cycle and why?
M phase- SHORTEST phase because the cell tends to minimize the time it spends with completely inactive (condensed) genome without the ability to transcribe it.
What are the checkpoints for Cell cycle control system?
Checkpoints for Cell cycle control:
- at end of G1, checkpoint: is the environment favorable ?(to be able to enter S phase).
- Between G2 and M phase, checkpoint: Is all DNA replicated? Is all DNA Damage repaired? (to enter Mitosis)
- towards end of M phase, Checkpoint: Are all chromosomes properly attached to mitotic spindle?
What is the duration of cell cycle stages proportional to?
Duration of cell cycle stages is proportional to amount of cells at certain stage in unsynchronized population.
list the duration of cell cycle stages from longest to shortest
Longest to shortest duration:
G1 phase, G2 phase, S, and M phase.
What are the two main factors that the Cell cycle control system depends on? Where did cell cycle control start from?
Genes responsible for cell cycle control first discovered in yeast, and includes CYCLIN (conserved protein factors) and CYCLIN-DEPENDENT PROTEIN KINASES (Cdks) that appear and disappear in cyclic manner (follow one another).
Described the kind of system that was used to decipher cell cycle control system in mammals.
using frog eggs as model system, helped decipher cell cycle control system.
Process:
- extracts taken from frog egg at different stages can trigger or stop normal cell cycle added in transition.
Ex: inject cytoplasm from M phase in cell- detect spindle and OOCYTE driven into M PHASE
-inject cytoplasm from interphase cell- OOCYTE DOES NOT ENTER M phase.
Described the kind of system that was used to decipher cell cycle control system in mammals.
using frog eggs as model system, helped decipher cell cycle control system for mammals.
Process:
- extracts taken from frog egg at different stages can trigger or stop normal cell cycle added in transition.
Ex: inject cytoplasm from M phase in cell- detect spindle and OOCYTE driven into M PHASE
-inject cytoplasm from interphase cell- OOCYTE DOES NOT ENTER M phase.
What regulates each phase of the cell cycle?
Each phase of the cell cycle is regulated by specialized CYCLIN- Cdk protein complex that regulates a different set of target proteins
ex: G1 and S- S cyclin; G2 and M phase- M cyclin.
Describe the major cyclins and CDKs of Vertebrates. What cyclin is used for mammals in G1 vs G1/S phase? Why is formation of G1/S complex most important?
G1 cyclins (Cyclins D1, D2 and D3 in mammals) form G1-Cdk complexes with Cdk4 and Cdk6 that drives cell through G1 phase. This complex manages events in phase G. The switch between G1 and S is mediated by G1/S-Cdk Complex made of Cyclin E and Cdk2. formation of the complexes is most important, as it is heavily influenced by environmental conditions, extracellular signals permit cells to divide.
How many D cyclins are in mammals?
Three D cyclins (D1, D2, and D3).
Describe what occurs during cyclic degradation?
Cyclins are destroyed by proteosomal pathway that drives the transition from one phase to the next. ANAPHASE- PROMOTING COMPLEX (APC) marks M-cyclin for degradation( by ubiquitylation of CYCLIN by APC/C) and takes cell out of mitosis.
The same APC complex destroys SECURIN and triggers separation of chromatids during ANAPHASE.
Describe how inhibitory kinases help control activity of cyclin-cdk complexes. what activates and inhibits complex?
Cdk protein concentrations in the cells increase gradually. To trigger abrupt activation of Cdk activity, Cdk comes in inactive, phosphorylated form. In this case, M cyclin, is phosphorylated by inhibitory kinase, Wee1. Removal of phosphate by phosphatase CDc25 activates the complex
How is activity of cyclin-Cdk complexes controlled by inhibitory signals? What kind of inhibitory signals?
When cyclin -cdk active, the activity of complex can be transiently delayed (paused) allowing cells to make a decision whether or not to move to next phase, for example from G1 to S.
Ex: inhbitory subunit p27 bind to cyclin-cdk complex and inactivate complex. Without subunit, and cyclin-Cdk complex it is active.
the activity of cyclin-cdk complex is controlled by both inhibitory subunits (p27) and inhbitory kinases (wee1)
What helps control the transition between cell stages?
presence of Cyclin-Cdk complexes control transition between the cell cycle stages.
ex: At first checkpoint(end of G1), CDK inhibitors block entry to S phase.
-at second checkpoint (between G2 and M), inhibition of activating phosphatase (cdc25) which blocks entry to mitosis.
at third checkpoint, (M phase), the inhibition of APC/C activation delays exit from Mitosis
what are mitogens and what are they useful for? What are other uses of mitogens? What would happen if mammalian cell has no mitogens?
Mitogens- external protein activator that triggers cell division.
Other uses; Mitogens serves as transcription regulators, but also TUMOR SUPPRESSORs that are normally Identified by absence in various tumors (since tumor cells tend to divide uncontrollably (devoid of those factors through selection process).
If deprived of transcription regulators called MITOGENS, mammalian cells would stay in G1.
Describe the signaling pathway of how mitogens trigger cell divison.
Pathway of mitogens triggering cell division:
- mitogen bind to mitogen receptor
- activated receptor leads to activation of intracellular signaling pathway in nucleus
- activation of G1-CDK and G1/S-Cdk leads to phosphorylation of Rb protein
- When Rb protein phosphorylated it is inactivated, which leads to activation of transcription regulator
- genes are then transcribed for entry into S-phase and cell division to occur.
what happens when Rb not phosphorylated? Rb active, transcription regulator inactive, no cell division.
What process can lead to arresting or halting cell cycle at G1 phase? How does p53 play a role in this process and what can occur if process goes wrong?
DNA damage can arrest the cell cycle at G1.
P53 is a major TUMOR SUPRESSOR protein that helps cells sense the DNA damage and temporarily halt the cell cycle at G1, until the DNA repair system is engaged.
Inability to repair DNA triggers p53 dependent APOPTOSIS (programmed cell death)
What processes are cyclin concentrations regulated by?
Cyclin concentrations are regulated by transcription and proteolysis
What major processes does the cell cycle control system trigger?
The cell cycle control system triggers division, tissue integrity and renewal.
What does the activity of cyclin-CDK complexes depend on?
activity of cyclin-CDK complexes depend on phosphorylation and dephosphorylation.
What phase of cell cycle, can Cdks be stabily inactivated?
G1 phase.
What two major things can S-Cdk initiate?
S-Cdk can initiate DNA replication and block re-replication.
What can arrest the cycle in G2 phase?
INCOMPLETE REPLICATION can halt or arrest cell cycle in G2 phase.
What controls the S-phase in cell cycle and how does it control it?
When can Prereplication complex initiate replication?
How does S-cdk trigger assembly of replisome
S-CDK complex controls S-phase.
In S-phase, S-CDK initiates replication and blocks repetition of replication
The pre-replication complex cannot initiate replication at ORI unless, it is activated by S-Cdk
S-Cdk phosphorylates Helicase, which triggers assembly of functional replisome (rep fork, DNA polymerase, etc)
What happens when replication is incomplete in S-phase of cell cycle?
If replication is incomplete in S-phase, the cell will be halted at G2 phase.
The presence of active replication prevents CDC25 from activation, which is necessary to dephosphorylate and thus activate M-Cdk
What happens to CDKs at the beginning of G1 in cell cycle and why does this occur?
When do you see the rise of cdks again?
ALL CDKS are 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 gene expression depletes cell from eventually all cdks completely ate end of mitosis. The rise of cdks start in G1 with accumulation of G1 cyclins that trigger transition to S phase.
How can cells delay division for prolonged periods?
by entering specialized nondividing states (G0).
What complex drives cell entry into M phase and mitosis and how does this complex amplify its activity?
M-CDK drives entry of cells into M phase and mitosis.
Activated M-Cdk self regulates (amplifies) its own activity by activating Cdc25 (positive feedback) and shutting down Wee1.
What occurs in the M phase of the cell cycle? what two major processes does M phase consist of?
What are the 5 stages mitosis is divided into?
In M phase, the division of a cell into two daughter cells occur.
M phase consists of nuclear division called MITOSIS, and cytoplasmic division called CYTOKINESIS.
Mitosis is divided into 5 stages : Prophase, Prometaphase, Metaphase, Anaphase, Telophase and Cytokinesis (PPMAT).
What major events occurs during interphase of cell cycle?
What occurs before replication and what kind of karyotype is present?
What karyotype is present after S phase?
What does n represent?
During interphase:
1. Centrosomes are duplicated
2. Tubulins and other proteins are synthesized, cell also increases in size.
3. DNA is replicated but is still in decondensed state.
4.Before replication, each chromosome has homologous pair (represented by two homologous chromosomes, each came from either father or mother)
This karyotype is called DIPLOID (2n)
n is a number of non-homologous chromosomes.
After S phase, each cell becomes TETRAPLOID (4n)
interphase is a preparation to M-phase (include g1, S, G2)
Describe the varying karyotypes and number of chromosomes for eukaryotic mammals, yeast, plants and also prokaryotes during mitosis
In MITOSIS for EUKARYOTES:
most eukaryotes: are 2n to 4n> 2n + 2n (DIPLOID)
some eukaryotes like YEAST are n to 2n > n + n (HAPLOID)
some eukaryotes: 2Xn to 4Xn > 2Xn + 2Xn (plants)
in BINARY DIVISION for PROKARYOTES
prokaryotes: n to 2n > n + n (BACTERIA)
What occurs during the prophase stage of mitosis?
What appears in the chromosomes?
Prophase is the first step of mitosis.
In prophase, the duplicated chromosome CONDENSE, outside nucleus, the MITOTIC SPINDLE forms between two centrosomes; CENTROSOMES move apart towards opposite sides and nuclear envelope is still intact.
The condensed chromosome have two sister chromatids held together by kinetochores.
What two cellular structures help configure duplicated chromosomes for SEGREGATION? How do these structures differ in functions and what activates these structures?
Cohesins and Condensins configure duplicated chromosomes for segregation.
Cohesin- tie together TWO SISTER CHROMATIDS and prevent them from breaking apart.
Condensin- help to COIL and thus condense EACH sister chromatid (one at a time)
Cohesins and condensin are structurally related and activated by M-Cdk.
what other cell division pathway are cohesions and condensins important in? what occurs when there is a defect in chromatid cohesion?
cohesions and condensins are important in MEIOSIS, which generates GAMETES.
Defects in sister chromatid cohesion leads to MISEGEREGATION and results in abnormal number of chromosomes (ANEUPLOIDY).
What cellular structure do microtubules form that is crucial for separation of sister chromatids and cytokinesis?
MITOTIC SPINDLE which is crucial for separation of sister chromatids and cytokinesis
What are the two transient cytoskeletal structures that mediate M phase in animal cells? How do microtubules attach to centromeres and what is their function?
what is the function of contractile ring?
MITOTIC SPINDLE AND CONTRACTILE RING mediate M phase.
microtubules of mitotic spindle attach to centromeres of sister chromatids through protein complex called KINTEOCHORE, and separate chromatids at beginning of ANAPHASE.
Contractile ring- composed of actin and myosin, help divide a cell into two cells, during cytokinesis.
Describe the structure of microtubules and how they extend and shrink. What occurs at plus end vs minus end?
Microtubules undergo constant polymerization and depolymerization (shrink) by addition and removal of tubulin alpha/beta heterodimers at PLUS end.
Plus end- is beta tubulin end (where add and remove dimers)
Minus end- “alpha end”, normally remains INTACT and attached to microtubule-organizing center (CENTROSOME)
What are the components of centrosome?
centrosome composed of pair of centrioles, centrosome matrix, and nucleating sites (increase number of microtubules in spindle)
