OCAMPO, Sheenalyn C.

FLORES, Nerissa P.

NOVENCIDO, Nizza J.

UMIPIG, Jerrilyn F.

Disorders And Diseases That Result From The Malfunction Of The Cell
During The Cell Cycle

Cell cycle checkpoint is a stage in eukaryotic cell cycle at which the cell
examines internal and external cues and decides whether to move forward with
cell division or not.

Key Points

 A checkpoint is one of several points in the eukaryotic cell cycle at which

the progression of a cell to the next stage in the cycle can be halted until
conditions are favorable.
 Damage to DNA and other external factors are evaluated at the G1
checkpoint; if conditions are inadequate, the cell will not be allowed to
continue to the S phase of interphase.
 The G2 checkpoint ensures all of the chromosomes have been replicated
and that the replicated DNA is not damaged before cell enters mitosis.
 The M checkpoint determines whether all the sister chromatids are
correctly attached to the spindle microtubules before the cell enters the
irreversible anaphase stage.

G1 Checkpoint

The G1 checkpoint determines whether all conditions are favorable for cell
division to proceed. The cell will only pass the checkpoint if it is an appropriate
size and has adequate energy reserves. At this point, the cell also checks for
DNA damage. A cell that does not meet all the requirements will not progress to
the S phase. The cell can halt the cycle and attempt to remedy the problematic
condition, or the cell can advance into G0 (inactive) phase and await further
signals when conditions improve. If a cell meets the requirements for the G1
checkpoint, the cell will enter S phase and begin DNA replication. This
transition, as with all of the major checkpoint transitions in the cell cycle, is
signaled by cyclins and cyclin dependent kinases (CDKs). Cyclins are cell-
signaling molecules that regulate the cell cycle.

The G2 Checkpoint

The G2 checkpoint bars entry into the mitotic phase if certain conditions are
not met. As with the G1 checkpoint, cell size and protein reserves are assessed.
However, the most important role of the G2 checkpoint is to ensure that all of
the chromosomes have been accurately replicated without mistakes or damage.
If the checkpoint mechanisms detect problems with the DNA, the cell cycle is
halted and the cell attempts to either complete DNA replication or repair the
damaged DNA. If the DNA has been correctly replicated, cyclin dependent
kinases (CDKs) signal the beginning of mitotic cell division.

The M Checkpoint

The M checkpoint occurs near the end of the metaphase stage of mitosis. The
M checkpoint is also known as the spindle checkpoint because it determines
whether all the sister chromatids are correctly attached to the spindle
microtubules. Because the separation of the sister chromatids during
anaphase is an irreversible step, the cycle will not proceed until the
kinetochores of each pair of sister chromatids are firmly anchored to at least
two spindle fibers arising from opposite poles of the cell.

P53 is a signaling protein, also known as tumor suppressor. It halts the cell
cycle at G1 when there is DNA damage.

P53 works on three roles.

1. First, it halts the cell cycle when it detects DNA damage.

2. Second, it activates DNA repairing enzymes.
3. If the damage is not fixable, it will carry out its third role which is to
program cell death so that the mutation will not be passed on.

The two external requirements for cells to divide

Cells follow external queues to start and stop dividing.

Contact inhibition – a regulatory mechanism that functions to keep cells

growing and dividing into a layer one cell thick.

Anchorage dependency - in order to divide; a cell must be anchored to a

surface or to other cells

Cancer cells disregard these external queues and proliferate continuously in

lumpy layers.

 Cancer starts when a single cell in a tissue is transformed by an

oncogene, a mutated gene; to a cancer cell in a process called
transformation.

The two different tumor types

Benign tumor - a mass of cells that retain adhesion proteins that keep them
properly attached to their home tissue. They have no potential to invade other
cells.

Malignant tumor - includes cells that enable them to spread to other tissues
and impair more organs of the body.