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CELL CYCLE IRAWAN YUSUF Department of Physiology Faculty of Medicine Hasanuddin University

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CELL CYCLEIRAWAN 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 cells 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

SCyclin + Cdk P53

G2 M

G1

Rb

Cell Cycle Is Regulated By Opposing Effects of Positive and Negative FactorsTumor Suppressor (P53, Rb) Cell death NORMAL Cell death Tumor Suppressor (P53, Rb) Oncogene (BCl2,BRCA1) Cell proliferation CANCER Oncogene (BCl2,BRCA1) Cell proliferation

Cyclins and Cyclin Dependent Kinases (Cdk)

Cyclin Cyclin D Cyclin E Cyclin A Cyclin A Cyclin B

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

Process regulated G1 phase progression G1 to S phase S phase progression S through G2 M phase

Waves of Cyclin-Cdk Activity Control The Cell CycleG1 S G2 M G1

Cyclin B-Cdk1

Kinase Activity

CyclinA-Cdk1 Cyclin E-Cdk 2 Cyclin D-Cdk 4/6

Time GF

CHECKPOINTS The cell cycle control system has checkpoints during G1, G2, S and M Checkpoint signals report cells status: Is the cell big enough? Is environment favorable? Is DNA replicated? Are chromosomes attached to opposite poles?

G1

S

G2

prophase

metaphase

anaphase

Cytokinesis

Mitosis