3 - siklus sel & pembelahan sel

CELL CYCLE

IRAWAN YUSUFDepartment of Physiology Faculty of Medicine

Hasanuddin University

CELL CYCLES

• The repeating sequence of growth and division through which cells pass each generation

• The purpose of the cell cycle is to allow cells to reproduce without alteration of genetic material

• The stages are well preserved between species

Why Do Cells Divide?

• Growth

• Development

• Maintenance

• Reproduction

Events of Cell Cycle

• G1 Phase - Period of growth; for many organisms this occupies a major portion of the cell’s life span

• S Phase – DNA replicates, resulting in duplicate chromosome

• G2 Phase – Cell prepares for division (mitosis), building necessary materials; centriole and other organelles double

• M Phase – Cell division, consisting of nuclear division and cytoplasmic division (cytokinesis)

Cell Cycle Progression

• Highly regulated process controlled by a large number of factors include:– Growth stimulating factors– Growth inhibiting factors– Enzymes that alter functional state of other proteins

by adding (kinases) or removing (phosphatases) phosphate groups

• Failure in the mechanisms by which the cell cycle is regulated can lead to uncontrolled cell growth and the development of cancer

The Cell Cycle Control

• There are important checkpoints during the cell cycle:– at the G1 – S transition– at the S – G2 transition– at the G2 – M transition

• Regulation of the cell cycle occurs as a consequence of cyclin – Cdk interaction

• Other proteins such as P53, Rb and oncogene play a role in regulating the cell cycle

• P27 : can block entry into S (synthesis) phase.

Cell Cycle Is Regulated By Opposing Effects of Positive and Negative Factors

S

G2 G1

M

Cyclin

Cdk

P53

Rb

+ -

Cell Cycle Is Regulated By Opposing Effects of Positive and Negative Factors

Tumor Suppressor(P53, Rb)

Oncogene(BCl2,BRCA1)

Tumor Suppressor(P53, Rb)

Oncogene(BCl2,BRCA1)

NORMAL

CANCER

Cell proliferation

Cell proliferation

Cell death

Cell death

Cyclins and Cyclin Dependent Kinases (Cdk)

Cyclin Cdk Process regulated

Cyclin DCyclin ECyclin ACyclin ACyclin B

Cdk 4,6Cdk 2Cdk 2Cdk 1(Cdc2)Cdk 1

G1 phase progressionG1 to S phaseS phase progressionS through G2M phase

Waves of Cyclin-Cdk Activity Control The Cell Cycle

G1 S G1G2 M

Cyclin D-Cdk 4/6

Cyclin E-Cdk 2

CyclinA-Cdk1

Cyclin B-Cdk1

GF

Kin

ase

Act

ivit

y

Time

CHECKPOINTS

• The cell cycle control system has checkpoints during G1, G2, S and M

• Checkpoint signals – report cell’s status:– Is the cell big enough?– Is environment favorable?– Is DNA replicated?– Are chromosomes attached to opposite poles?

G1 G2S prophase metaphase anaphase Cytokinesis

Mitosis