Cell Cycle

Front 1

What is a cell cycle?

Back 1

The events from one cell division to the next

Front 2

What are the four phases of the cell cycle?

Back 2

-G1 The gap between M (mitosis) and S ~time varies
-S DNA synthesis occurs in this period. ~ 6-8 h
-G2 Gap between S and M. ~ 2-6 h
-M Mitosis ~ 1 h
>Begins with chromosome condensation
>Ends with cell division

*RNA and protein synthesis occurs at each phase.

*Senescent (old) cells exit the cell cycle in G1 and are said to be in G0. They can be stimulated to re-enter the cell cycle. e.g. by addition of required growth factors.

Front 3

What are the steps of Mitosis?

Back 3

1. Interphase: Nuclear membrane breaks down
2. Prophase: Chromosomes condense and become visible
3. Prometaphase/ Metaphase: Microtubules bind and align chromosomes
4. Telophase/ AnaphaseChromosomes separate
5. Cytokinesis : Nuclear membrane reforms and cells divide

Front 4

How do cyclins regulate passage through G1?

Back 4

-passage through G1 is regulated by cyclins D and E

Front 5

What is so important about the start point of the cell cycle?

Back 5

important checkpoint (restriction point)

commits the cell to enter S phase and DNA synthesis

Front 6

What are the controls on cell divsion

Back 6

-Growing cells divide once with each doubling of mass and size. --Cells maintain the same average size over many generations.
-DNA must replicate only once with each cell division.
>Once DNA replication has started, it must be completed.
>Chromosome separation in mitosis must not begin until all -the chromosomes are attached to microtubules and properly aligned.
>The cell must not divide before DNA replication is complete.
-If DNA is damaged it must be repaired before replication.
-A differentiated cell must not resume replication or cell division.

Front 7

How does a cell enter mitosis?

Back 7

Entry into M phase requires M-phase-promoting factor (also known as maturation promoting factor) (MPF), which consists of a protein kinase called the cyclin-dependent protein kinase (Cdk1) and regulator protein cyclin B.

Cdk1 protein kinase is present throughout the cell cycle but is only active when complexed with cyclin.

Cyclin B accumulates until the middle of mitosis. Then it is rapidly degraded so that mitosis will not occur again until the next cell cycle.

Active MPF phosphorylates several target proteins, including histones, resulting in chromosome condensation, and the nuclear lamins, resulting in nuclear envelope break down. This allows cell division to proceed

Front 8

What is Rb?

Back 8

A critical cell cycle regulator is the retinoblastoma protein (Rb), a tumor-suppressor that is absent in retinoblastoma, a cancer of the eye that affects children.

Front 9

How does Rb work?

Back 9

-Rb binds and inhibits E2F, a transcription factor responsible for the production of many genes involved in DNA synthesis.

-When Cdk1 kinase is activated, it phosphorylates Rb, which releases E2F. Once released, E2F is active.

-In tumors, the Rb gene becomes mutated, the protein is inactive or not expressed, and so it no longer prevents E2F activity, DNA synthesis, and cell cycle progression

Front 10

What stimulates cell division?

Back 10

Many growth factor hormones are mitogens: they stimulate senescent (non-dividing) cells to re-enter the cell cycle. If this occurs at the wrong time or place, the cells can form a tumor.

Front 11

What is the p53 protein?

Back 11

-cell cycle regulator
-tumor suppressor absent in many cancers

Front 12

What actions do p53 take when there is damage to DNA?

Back 12

p53 prevents entry into S phase until the DNA is repaired. If the damage is excessive, p53 will trigger apoptosis (programmed cell death).

Front 13

What happens to p53 in tumors?

Back 13

In many tumors, the p53 gene becomes mutated
-the protein is inactive or not expressed, and so it no longer prevents progression through the cell cycle after DNA damage.

-If damaged DNA is replicated, tumors accumulate more mutated DNA, and the cancerbecomes more aggressive

Front 14

Tumor suppressor gene Rb

Back 14

A critical cell cycle regulator is the retinoblastoma protein (Rb), a tumor-suppressor that is absent in retinoblastoma, a cancer of the eye that affects children.

Rb binds and inhibits E2F, a transcription factor responsible for the production of many genes involved in DNA synthesis.

When Cdk1 kinase is activated, it phosphorylates Rb, which releases E2F. Once released, E2F is active.

In tumors, the Rb gene becomes mutated, the protein is inactive or not expressed, and so it no longer prevents E2F activity, DNA synthesis, and cell cycle progression.

Front 15

Tumor suppressor gene p53

Back 15

Another key cell cycle regulator is the p53 protein, a tumor-suppressor absent in many cancers.

If there is DNA damage, p53 prevents entry into S phase until the DNA is repaired. If the damage is excessive, p53 will trigger apoptosis (programmed cell death).

In many tumors, the p53 gene becomes mutated, the protein is inactive or not expressed, and so it no longer prevents progression through the cell cycle after DNA damage.

If damaged DNA is replicated, tumors accumulate more mutated DNA, and the cancer becomes more aggressive.

Front 16

define confluent monolayer

Back 16

Normal cells will grow until they cover the bottom of the petri dish forming a confluent [used all the space] monolayer

Front 17

What is density-dependent inhibition growth?

Back 17

contact inhibition


The cells can be triggered to divide again with additional growth factor or removing some of the cells.

Front 18

define sensecent

Back 18

After about 50 cell divisions the cells will stop dividing and the cultures become senescent. [cells are still alive but they have stopped dividing]

Front 19

What does the number of divisions at which scencence occurs depend on?

Back 19

Age of individual from which the cells were obtained.

Cells from an embryo will undergo more divisions than cells from an adult.

Front 20

How can cells be transformed?

Back 20

Cells can be transformed by chemical carcinogens or by infection with cancer-causing tumor viruses. Cells taken directly from tumors also appear to be transformed.

immortal cells are usually transformed

Front 21

what are characteristics of a transformed cell.

Back 21

1. Decreased adhesion to other cells [less sticky, loose, have a weird shape] makes it more likely to travel to other parts of body
2. Loss of contact inhibition
3. Decreased anchorage dependence (i.e., will grow without adhering to a surface). Can lead to metastasis, or the spread of cancer to other organs within the body. [don’t need signal to undergo cell division]
4. Decreased requirement for serum growth factors
5. May cause [cancerous] tumors if injected into appropriate host animal
6. Altered appearance, altered gene expression, altered metabolism.

Front 22

What are immortal cells called?

Back 22

Occasionally, cells become immortal - they continue to divide forever. Such cells are called a cell line. Cell lines are very useful experimentally and still show most of the growth characteristics of the original cells. [have little inhibition, have contact inhibitions but you know that something is wrong with them and that they are precancerous]

Front 23

At what phase(s) does the nuclear membrane breaks down?

Back 23

Interphase/Phophase

Front 24

At what phase(s) does the chromosomes condense and become visible?

Back 24

Prophase/Prometaphase

Front 25

At what phase(s) do microtubules bind and alight chromosomes?

Back 25

Prometaphase/metaphase

Front 26

At what phase(s) do chromosomes separate?

Back 26

anaphase/telopphase

Front 27

At what phase(s) does the nuclear membrane reform and cells divide?

Back 27

cytokinesis/ daughter cells

Front 28

define nuclear envelope

Back 28

the membrane that separates the contents of the nucleus (mostly DNA) from the cytosol.

Front 29

define chromosome

Back 29

a single large molecule of DNA.

Front 30

define microtubule

Back 30

are part of a structural network (the cytoskeleton) within the cell. They are capable of growing and shrinking in order to generate force including force needed to separate duplicated chromosomes during cell division

Front 31

define centriole

Back 31

is the main microtubule organizing center within the cell.

Front 32

define chromatid

Back 32

one-half of a duplicated chromosome joined at centromeres.

Front 33

What is the main function of tumor suppressor genes?

Back 33

To prevent passage through the restriction point

Front 34

When is the protein kinase activity of Cdk1 at its highest?

Back 34

highest at M where it binds to proteins as part of a large complex

Front 35

How do cyclins regulate passage through S phase?

Back 35

Passage through S phase is regulated by cyclin A.

Front 36

define apoptosis

Back 36

programmed cell death

Apoptosis is an important mechanism for the construction of many organs. Initially, apoptosis was observed in the course of organ remodeling during development (embryogenesis). For example, during development of the brain, many more neurons die than are eventually used to generate this organ.

Like cell division and development, apoptosis is carefully regulated by growth factors. If apoptosis fails to occur at the right time in this process, birth defects will occur.
 

Front 37

define necrosis

Back 37

accidental cell death