CELL CYCLE

BLOK BBS-1 Alya Amila Fitrie Radita Nur Anggraini Ginting Medical School University of Sumatera Utara Medan 2011

Where a cell arises, there must be a previous cell, just as animals can only arise from animals and plants from plants.
Rudolf Virchow (German pathologist) in 1858

The mammalian cell cycle

WHAT IS CELL CYCLE?

A cell reproduces by performing an orderly sequence of events in which it duplicates its contents and then divides in two. This cycle of duplication and division, known as the CELL CYCLE, is the essential mechanism by which all living things reproduce. DNA must be replicated accurately

The regulation of the cell cycle must ensure that the events in each phase is complete before moving to the next check points are important

WHAT IS CELL CYCLE?

In multicellular species, long complex sequences of cell division are required to produce a functioning organism. Even in the adult body, cell division is usually needed to replace cells that die.

In fact, each of us must manufacture many millions of cells every second simply to survive: if all cell division were stoppedby exposure to a very large dose of x-rays, for examplewe would die within a few days.

WHAT IS CELL CYCLE?

The details of the cell cycle vary from organism to organism and at different times in an organism's life.
Certain characteristics, however, are universal.

The minimum set of processes that a cell has to perform are those that allow it to accomplish its most fundamental task: the passing on of its genetic information to the next generation of cells.

INTERPHASE
Interphase generally lasts at least 12 to 24 hours in mammalian tissue. During this period, the cell is constantly synthesizing RNA, producing protein and growing in size.

Interphase : divided into 4 steps: Gap 0 (G0), Gap 1 (G1), S (synthesis) phase, Gap 2 (G2).

GAP 0 (G0)

There are times when a cell will leave the cycle and quit dividing. This may be a temporary resting period or more permanent. An example of the latter is a cell that has reached an end stage of development and will no longer divide (e.g. neuron).

GAP 1 (G1)

Cells increase in size in Gap 1, produce RNA and synthesize protein.

An important cell cycle control mechanism activated during this period (G1 Checkpoint) ensures that everything is ready for DNA synthesis. (ref: cells alive)

S- PHASE

To produce two similar daughter cells, the complete DNA instructions in the cell must be duplicated. DNA replication occurs during this S (synthesis) phase.

GAP 2 (G2):

During the gap between DNA synthesis and mitosis, the cell will continue to grow and produce new proteins. At the end of this gap is another control checkpoint (G2 Checkpoint) to determine if the cell can now proceed to enter M (mitosis) and divide.

MITOSIS OR M PHASE:

Cell growth and protein production stop at this stage.

The cell's energy is focused on the complex and orderly division into two similar daughter cells.

Mitosis is much shorter than interphase, 1-2 hours. There is a Checkpoint in the middle of mitosis (Metaphase Checkpoint) that ensures the cell is ready to complete cell division.

MITOSIS
Profase
the chromosomes become visible and condense, becoming shorter and thicker and form sister chromatid The nuclear envelope breaks dowmn and spindle fibers form as microtubules grow out of the centrioles that move to opposite poles of the cell

Metafase
the double stranded chromosomes line up along the equator of the cell The spinde now fully formed and the microtubules attach to each sister chromatid

Anafase
the sister chromatids of each chromasome begin to separate
The centromere that holds sister chromatids together devides and the chromosomes move away from each other along its spindle fiber

Telofase, the two groups of chromosomes reach the opposite ends of the cell. As a new nuclear envelope starts to form around each group,the chromosomes uncoil and the spindle dissappears

CYTOKINESIS

The division of the cytoplasm and organelles is called cytokinesis or the C phase

The result of mitosis and cytokinesis is the formation of two genetically identical cell

IMPORTANT NOTE FOR CELL CYCLE

There is a critical checkpoint in the mammalian cell cycle, called Restriction Point (R) Prior to R, the cell depends on external stimuli (growth factor) to progress through G1 After R, the cell become independent of external mitogenic stimuli and can complete the cell division cycle autonomously.

CELL CYCLE REGULATION

3 principle checkpoints are in G1, G2 and M

G1 (START/restriction point): should DNA be replicated? G2 : quality control: is DNA replicated and in good condition? M: are chromosomes lined up correctly?

CELL CYCLE CONTROL

As with most enzyme regulation throughout the cell, enzyme control of the cell cycle is mediated in the nucleus through
kinases (enzymes that activate other proteins by the addition of phosphate groups) and phosphatases (enzymes that remove phosphate groups from proteins).

The kinases controlling the cell cycle are called Cyclin-Dependent Kinases (cdks), socalled because they cannot act without being conjoined to a cyclin protein.

DIFFERENT CYCLIN-CDK DURING CELL CYCLE

Different cyclins (designated by letters A,B,D,E) are present in different levels during different phases of the cell cycle The cyclins were named in the order in which they were discovered, so there is no logical relation between the letter and the cell cycle phase.

Similarly, the cdk enzymes are designated by number (cdk4, cdk2, cdk1) according to when they were discovered.

CYCLIN
Cyclins are named cyclins because their appearance during the cell cycle is cyclical. The 1st cyclin synthesis in response to growth factor stimulatory signal is cyclin D Mid G1, cyclin E followed by cyclin A at G1 to S transtition. Cyclin B at G2 and M phase.

The periodicity of cyclin is mediated by their synthesis and subsequent proteolysis degradation by ubiquitin/proteasomes when their services are no longer required.

WHY ARE THE RELATION BETWEEN CANCER AND CELL CYCLE?

Cancer, result from multiple genetic alteration in genes that control:

proliferation differentiation programmed cell death (apoptosis)

Many genes that are mutated in human cancer, directly involved in regulation of the cell division cycle, they are linked to the machinery that controls cell proliferation. Two groups of cancer genes

oncogenes, mutated version of genes, normal function is to stimulate cell proliferation tumor suppressor genes, normally restrict growth

Summary

Thank you...