Cell cycle is ordered process producing identical daughter cells
cell size control
coordination of events
: enter M phase only after replicating DNA; Do not re-replicate DNA unless cell has divided
choice to enter cell cycle
: highly regulated
Þ are there enough nutrients; is there enough room to grow and divide (contact inhibition); growth factors - signaling; developmental choice(have cell cycle); loss of cell cycle control (cancer)
Length of cell cycle: 10-30 min (for some developing embryos); 24 hrs (fibroblast); >1 yr (mammalian liver cell)
Phases of the Cell Cycle
2 parts
Þ interphase and mitosis
Interphase
synthesis of organelles and DNA
G1 (gap 1)
Þ 6 – 12 hr; interval btwn last M phase and DNA synthesis
(G1): after a cell passes; it’s committed to complete the cell cycle
Regulation of the Cell Cycle
MPF (mitosis promoting factor): stimulates a cell at any stage to undergo mitosis
SPF (S phase promoting factor): promotes G1 cell to replicate its DNA
check point control: won’t enter M phase until DNA is replicated
did not promote G2 cells to replicate DNA; once DNA is replicated, there is a block to re-replication
Other checkpoint controls occur when cells are exposed to irradiation, mutagens, or certain drugs
G1 cell will not pass restriction point until its DNA is repaired
G2 cell will not enter M phase until its DNA is repaired
Many human cancers have defects in the checkpoint control system
protein p53 checkpoint control gene: mutation allows G1 cell with DNA damage to pass the restriction pt. before repair
Cyclins and Cyclin-Dependent Kinases (CDK’s)
Regulation of passage into each stage of the cell cycle is mediated by reversible phosphorylation of substrates required at that particular stage of the cycle by a dimeric protein composed of cyclin-dependent ser/thr kinase (CDK) and an associated protein cyclin
Specific CDKs and cyclins regulate each phase (MPF = CDK2 + cyclin B)
CDK + cyclin = active (phosphorylates)
Once substrate moves past the regulation point, phosphatases remove the phosphate returning it to its normal state
Until cyclin is destroyed, CDK kinase remains active and the cell will not be able to pass into the next stage
Rb
Rb binds and halts movement thru cycle
Þ cyclins arise and bind to CDK, CDK/cyclin complex phosphorylates Rb which detaches allowing movement thru the cell division cycle