BI203 Lecture 23: The Cell Cycle - Stages of Cell Cycle/Checkpoints (Slides 1 - 19) Flashcards
The 3 signaling pathways which can regulate cell proliferation:
cAMP pathway, PI 3-kinase/Akt pathway, ERK MAP Kinase pathway
In eukaryotic cells, progression through the cell cycle is controlled by ___ ___ that have been conserved from yeasts to mammals.
Defects in cell cycle regulation are a common cause of the abnormal proliferation of ___ cells.
protein kinases, cancer
Bacteria do ___ have a cell cycle. They instead replicate DNA and divide about once every 20 min.
NOT
The Eukaryotic cell cycle has ___ phases.
4
The 4 phases of the Eukaryotic Cell Cycle:
M, G1, S, G2
___ phase - Nuclear division, usually ending with cell division (cytokinesis).
M (mitosis) phase
___ phase - Interval between mitosis and DNA replication. The cell is metabolically active and growing.
G1 (gap 1) phase
___ phase - DNA replication takes place.
S (synthesis) phase
___ phase - Cell growth continues; proteins are synthesized in preparation for mitosis.
G2 (gap 2) phase
___ - Period between mitoses, divided into G1, S, and G2.
Interphase
A major control point called ___ controls progression from G1 to S, first defined in yeast cells.
Once a yeast cell pass ___, they are committed to entering S phase and undergoing one division cycle.
START
Passage through START is highly regulated by external signals, such as ___ availability and cell ___.
If there is a shortage of nutrients, yeast cells can arrest the cycle at START and enter a resting phase.
In order to maintain constant size, yeast cells must reach a minimum ___ to pass START.
nutrient, size, size
In most animal cells, the ___ ___ in late G1 functions like START. Once it has passed the ___ ___, the animal cell is committed to proceed through S phase and the rest of the cell cycle.
restriction point
If appropriate growth factors are not present in G1, progression stops at the restriction point and animal cells enter a resting stage called ___.
G0
Skin fibroblasts, for example, are arrested in ___ until stimulated by platelet-derived growth factor to proliferate and repair wound damage.
G0
Coordination of the cell cycle phases is dependent on a series of ___ ___ ___. They prevent entry into the next phase until events of the preceding phase have been completed.
cell cycle checkpoints
___ ___ ___ ensure that damaged DNA is not replicated and passed on to daughter cells. The cell cycle is then arrested until DNA is repaired or replicated.
DNA damage checkpoints
The ___ ___ ___ ensures that all chromosomes are
aligned on the metaphase plate before cell divides.
spindle assembly checkpoint
The spindle assembly checkpoint stops mitosis at ___ if chromosomes are not properly aligned on the spindle.
metaphase
___ ___ (Cdk’s) and ___ together control progression through all phases of the cell cycle.
cyclin-dependent kinases (Cdk’s), cyclins
___ = Family of kinases that promote cell cycle progression when active.
Cdk’s
___ = Family of regulatory subunits required for catalytic activity of Cdk’s.
cyclins
The first identified Cdk/cyclin = ___/___ ___, aka ___
Cdk1/cyclin B, aka MPF
MPF was discovered during studies of frog egg (= big cells) ___.
maturation
Studies of frog oocytes, which are arrested in G2 until hormonal stimulation triggers entry into M phase.
In 1971, researchers found that oocytes could be induced to enter M phase by microinjection of cytoplasm from oocytes that had been hormonally stimulated.
The responsible cytoplasmic factor from G2 cells was called ___ ___ ___ (MPF).
maturation promoting factor (MPF)
___ = Kinase whose activity induces entry into meiosis.
Cdk1
___ ___ = Regulatory protein required for Cdk1 kinase activity.
Cyclin B
MPF activity is required in ___ ___ ___ for progression from G2 to M.
all eukaryotic cells
Cells synthesize Cyclin B throughout the cell cycle, during which it accumulates to “threshold levels” at the end of ___. This stimulates MPF activity.
G2
Cyclin B can be ___ and ___, causing inactivation of Cdk1 and an exit from M phase.
ubiquitylated, degraded
Ubiquitylation of cyclin B is mediated by a ubiquitin ligase: ___/___
APC/C
Once any cyclin has induced its necessary progression in the cell cycle, it is then ___ by a ___.
degraded, proteasome
MPF activity can also be regulated by ___. The Cdk1/cyclin B complex is ___ by a kinase, deactivating the complex.
phosphorylation, phosphorylated
Inhibitory proteins of Cdk’s: ___ ___ (CKIs)
There are 2 families in animal cells: Ink4 and Cip/Kip
Cdk inhibitors (CKIs)