Mitosis and Cell Cycle Flashcards
Goal of somatic cell cycle
The goal of the somatic (mitotic) cell cycle is to produce two cells that are genetically identical to the original cell.
Cell cycle phases
The cell cycle is divided into four phases-
S phase in which chromosome synthesis (replication) occurs,
M phase in which chromosome segregation occurs.
G1 and G2 are gap phases that precede S and M phases, respectively.
Regulation occurs in G1 and G2 phases. In G1 phase, cell growth is coordinated with cell division at the “R” (restriction point). So you only divide if you are big enough!
Cyclin Dependent Kinase
CDK is an enzyme that is a protein kinase. The CDK subunit is inactive and requires binding of the CYLCIN subunit for ACTIVITY.
It is cyclin protein levels that change (CDK levels are constant) to regulate CDK activity during the cell cycle. Another level of regulation is the binding of CDK inhibitors.
Cyclin levels oscillate to produce diff. phases of cell cycle. This is how you prevent re-replication.
Retinoblastoma protein
An inhibitor of the cell cycle-when cells divide, CDK’s INHIBIT RB (a double-negative)… allowing cycle to proceed
Rb is known tumor suppressor in that loss of Rb results in tumors in retinoblastoma and also in other cancers (e.g. small cell lung cancer).
CDI’s (CDK inhibitors)
there are two classes-Cip/Kip and INK4:
p21 (Cip) and p27 (Kip) will inhibit all CDKs
while p15 and p16 (INK4) are specific to CDK4/6-cyclinD complexes.
The p16 CDI is also a tumor suppressor in melanoma and other cancers (e.g. non-small cell lung cancer, head and neck cancer).
Mitogens
Mitogens or GFs eventually will cause the production of cyclin D1-3 that ACTIVATES CDK4/6 to INHIBIT Rb, (allowing cell cycle to progress)
Mitogens act at the cell surface and ultimately cause an increase in cyclin D1 transcription.
Mitogen –> cyclin D1-3 –> activate CDK4/5–> INHIBIT RB—> cell cycle!
Replication Bubble
Replication begins at discrete sites called origins. The human genome has about 100,000 origins.
Replication proceeds bidirectionally from these origins. Only a small subset of origins are used in somatic cells, while a much larger number is used in embryos to increase the rate of replication and reduce the length of S phase. Thus, replication is always regulated at the origin or initiation level.
SO YOU CAN have more replication/higher rate if you use more origins.
Pre-RC formation
These are multiprotein complexes that are loaded onto the origins in G1 phase.
A major protein in these complexes is the MCM DNA helicase, which opens open the DNA helix for replication after it is ACTIVATED BY S-CDK complexes (s phase)
Why do we care about pre-RC?
The pre-RC cycle prevents re-replication and assures that S phases are always followed by an intervening M phase-
The pre-RC can only be loaded onto origins in G1 phase. The pre-RC can only be activated in S phase.
Thus, you cannot load and activate pre-RCs in the same phase, thereby preventing re-replication.
In G1 you have LOW CDK so allows for building of pre-RC. S phase has high CDK so you activate replication and prevent any more pre-rc building. Driven by CDK’s.
How do you activate the pre-RC in S phase?
requires two protein kinases-CDK with cyclins E and A (S-CDK) and Cdc7-Dbf4 kinases (also known as DDK=Dbf4-dependent kinase).
Combined action of S-CDK and DDK result in MCM helicase activation and loading of the replication complex that contains the DNA polymerases and other replication enzymes.
