Cell Division Cycle

Introduction

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

S phase Þ 6 – 8 hr; DNA is replicated (4n)

G2 (gap 2) Þ 3 – 4 hr; interval btwn S phase and M phase

Mitosis (M phase) Þ 30 – 60 min

G_o phase Þ cell exits cell division cycle completely (non-dividing cell)

contact inhibition, neuronal cells

cancer: from G_o Þ enters cell cycle

Restriction point (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 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