H31/100624/2017

1. Describe the cell cycle, using appropriate diagrams.

The cell cycle is the series of events that take place in a cell leading to its division and
replication (duplication) that produces two daughter cells. Two separate events usually occur
during cell division. This include the events of mitosis (cell cleavage) and synthetic activity which
leads to doubling of the cell constituents enough for the two newly formed daughter cells(1).
Mitotic cell cycle involves 2 main stages: interphase and division/ M phase.

Interphase/resting phase

The cell grows in size and prepares itself for the next division. It is the middle stage of one cycle
and occurs between two division phase. It is further divided into 3 stages.

i. G1 phase/ pre DNA synthesis phase

It is the longest sub stage of cell cycle taking place in up to 12 hours. The number
of cell organelle increase in size as different types of RNA and proteins are rapidly
being synthesized by the cell.

ii. S- Phase
Takes place in about 6-10 hours. Nuclear
DNA replicates and histone proteins are
synthesized. New DNA molecules formed
are not distinct but intertwined. Replication
of centriole takes place in this stage
iii. G2 Phase/ post DNA synthesis phase/
pre-mitosis Phase
Takes place in about 3-12 hours. Number
of cell organelles increase and special
materials necessary for cell division are synthesized i.e. tubulin proteins which are
required for spindle fiber formation. Cells store ATP in this phase which is energy
required for cell division.

Mitotic Phase
Chromatin condenses into chromosomes which line up along metaphase plate. Chromosomes
break at centromeres and sister chromatids move to the opposite polar ends of the cell. Takes
place in 4 stages: prophase, metaphase, anaphase, telophase.

Cytokinesis/C phase

It is the division of the cytoplasm to form 2 daughter cells. Myosin 2 and actin filament forms a
ring at the equator and contract to cleave the cell into two.

2. Describe the mechanisms of cell cycle regulation.

Cyclin dependent kinases which remove a phosphate group from ATP and add to another
protein are activated when combined with cyclin. There are checkpoints G1→S and G2→M
where a kinase enzyme combines with cyclin(2). This signals progression in the cycle.

 S Kinase is capable of starting DNA replication after interaction with S-cyclin (at
G1→S checkpoint). The cyclin is then destroyed rendering the kinase inactive.
 M Kinase is capable of turning on mitosis after interacting with M cyclin at G2→M
checkpoint.

3. Describe the mechanisms of quiescence (Go state).

This is a reversible, dormant state of a cell with minimal basal activity. Various mechanisms
which contribute to this state include:

 Decreased concentration of cyclin D

 Hypo-phosphorylation of Rb protein (active form)

Therefore, the above mechanisms hold the cell cycle at check point 1 by inhibiting the
expression of several transcription proteins that codes cyclins A and E which are necessary for
cell cycle progression(3).

4. Describe the mechanisms by which cells exit the quiescent (Go) state

Differentiation signals can transcriptionally regulate CKIs to trigger cell cycle exit. Signals from
extracellular growth factors bind to receptors on cell surface. Cyclin D proteins are recruited
which act as a mitogenic signal therefore promoting progression of cell cycle(4).

References
1. Suryadinata R, Sadowski M, Sarcevic B. Control of cell cycle progression by
phosphorylation of cyclin-dependent kinase (CDK) substrates. Bioscience Reports. 2010
Mar 17;30(4):243–55.

2. Ding L, Cao J, Lin W, Chen H, Xiong X, Ao H, et al. The Roles of Cyclin-Dependent Kinases
in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer. Int J Mol Sci
[Internet]. 2020 Mar 13 [cited 2021 Feb 1];21(6). Available from:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139603/

3. Shackelford RE, Kaufmann WK, Paules RS. Cell cycle control, checkpoint mechanisms, and
genotoxic stress. Environ Health Perspect. 1999 Feb;107(Suppl 1):5–24.

4. Dhawan J, Laxman S. Decoding the stem cell quiescence cycle – lessons from yeast for
regenerative biology. J Cell Sci. 2015 Dec 15;128(24):4467–74.