3.1-3.2 Cell cycle in eukaryotic cells

Cell cycle

• Phases a cell passes through to produce daughter cells by cell division

Interphase

• It’s everything except mitosis and cytokinesis.

• Have phases within it

• These phases are:

G1, G0, S

• duration of time is highly variable

G1 phase

• each chromosome is a single unreplicated DNA molecule

• Duration of time spent in this phase varies from minutes to years

• Some cells can enter a G0 phase

• Ends at the G1-S transition, where commitment to cell division is made

S phase

• DNA replication occurs

• Each chromosome is replicated through DNA replication, producing sister chromatids

• The sister chromatids remain together until mitosis

G2 Phase

• The cell prepares for mitosis

• synthesizes the structures needed to move the chromatids to oppoosite ends of the cell

M Phase

• Includes mitosis + cytokinesis

• Nuclear division occurs during mitosis

• The cytoplasm is divided and cell division occurs during cytokinesis

G0 phase

• A resting phase that cells may enter during G1 instead of continuing past the restriction point to commit to cell division, ( moving onto S phase)

• Cells can enter for three main reasons

i) differentiation - neurons

ii) nutrient or signal limitation - poor environmental conditions

iii) contact inhibition - prevents overgrowth

Restriction point (R)

• Controlled by the G1/S cyclin - CDK

• Once this point is passed the cell is committed to cell division and can not go back

Enzymes 

• speed up biochemical reactions by bringing reactants together

• Reactants are called substrates

• Substrates bind to the active site of the enzyme 

• Binding forms the enzyme-substrate complex

Kinases

• An enzyme that catalyzes the transfer of a phosphate group from ATP to another molecule (usually a protein), a process called phosphorylation

Cell cycle checkpoints

• Points of transition in between different phases of the cell cycle

• These points are regulated by cyclin-CDKs

• checkpoints serve as control mechanisms to make sure the cell cycle is progressing properly

Cyclin-dependent kinases ( CDKs)

• Not active unless bound to a cyclin protein

• binding to a cyclin exposes its active site 

• The substrate can then bind to the active site

• the phosphorylated substrate then regulates cell cycle events 

• there are multiple different cyclin-CDK complexes in the cell, each acting at different stages in the cell cycle

Cyclins

• are present cyclically

• only made at certain times in the cell

What happens if cyclins are underproduced when needed?

• CDKs remain inactive, checkpoints can’t be passed, and the cell is halted

• DNA replication or mitosis won’t occur, slowing or stopping cell division.

G1/S transistion cyclin-CDK

• controls the cell cycle checkpoint known as the restriciton point

• The G1/S cyclin-CDK catalyzes the phosphorylation of retinoblastoma protein(RB)

• RB is active when unphosphorylated

The cell can not move through the restriction point when RB is active

• RB is inactive when phosphorylated

The cell can move through the restriction point when RB is inactive

Why would mutation and inactivation of RB contribute to cancer?

• A mutation or inactivation of Rb removes the cell’s ability to halt the cycle at the G1/S checkpoint, allowing cells to enter S phase and divide uncontrollably

• This loss of regulation leads to unchecked cell proliferation, a key feature of cancers