Why do different cell types' rates of the cell cycle differ? The cell cycle is swiftly completed by injured or lost cell types to produce replacements. Adult skin and digestive tract cells go through the cell cycle quite fast, whereas nervous system cells divide very seldom. Cells divide regularly during embryonic development, perhaps as frequently as once or twice an hour, moving through the cell cycle very quickly. What is the cell cycle? The regular sequence of activities that cells go through as they develop and divide is known as the cell cycle. Prokaryotic cells go through a rapid cycle of cell division, DNA replication, and expansion. In prokaryotes, cell division occurs in a single stage known as binary fission (shown right).Compared to prokaryotic cells, eukaryotic cells have a more complicated cell cycle. How is the eukaryotic cell cycle divided? Interphase is the period between cell divisions. Depending on the kind of cell, the interphase might be shorter or longer. The three stages or phases of the eukaryotic interphase are G1, S, and G2. The M phase of the cell cycle is when eukaryotic cells divide. Mitosis and cytokinesis are the two stages that make up the M phase. What happens during each phase of eukaryotic interphase? G1: Cells do most of their growing during this phase. It begins when mitosis is complete and ends when DNA replication begins. S: DNA is synthesized as chromosomes are replicated. G2: Many of the molecules and cell structures required for cell division are produced; usually the shortest phase of the cell cycle. What happens during the M phase of the eukaryotic cell cycle? The M phase is usually much shorter than interphase and results in two daughter cells. The first step of the M phase is mitosis. The cell’s nucleus divides during mitosis. The second step of the M phase is cytokinesis, during which the cell’s cytoplasm is divided. What are the steps of mitosis? Mitosis consists of four steps: prophase, metaphase, anaphase, and telophase. Prophase: nuclear envelope breaks down, DNA condenses, spindle begins to form. Metaphase: replicated chromosomes, which appear as paired sister chromatids, line up across the center of the cell and attach to spindle. Anaphase: sister chromatids separate and move toward ends of the cell. Telophase: chromosomes disperse, nuclear envelope reforms. What completes the M phase of the cell cycle? Cytokinesis completes the M phase of the cell cycle. It may begin while telophase is still taking place. During cytokinesis, the cytoplasm (which includes all of the contents of a eukaryotic cell outside the nucleus) draws inward, eventually pinching off into two nearly equal parts. Each part contains a nucleus. In plant cells and other eukaryotic cells that have a cell wall, a cell plate forms halfway between the divided nuclei. It gradually develops into cell membranes and forms a complete cell wall surrounding each daughter cell. Upon the completion of cytokinesis and the M phase, a

1. CELL CYCLE

2. Why do different cell types' rates of
the cell cycle differ?
•The cell cycle is swiftly completed by injured or lost cell
types to produce replacements.
•Adult skin and digestive tract cells go through the cell cycle
quite fast, whereas nervous system cells divide very seldom.
•Cells divide regularly during embryonic development,
perhaps as frequently as once or twice an hour, moving
through the cell cycle very quickly.

3. What is the cell cycle?
•The regular sequence of activities
that cells go through as they develop
and divide is known as the cell cycle.
Prokaryotic cells go through a rapid
cycle of cell division, DNA replication,
and expansion. In prokaryotes, cell
division occurs in a single stage
known as binary fission (shown
right).Compared to prokaryotic cells,
eukaryotic cells have a more
complicated cell cycle.

4. How is the eukaryotic
cell cycle divided?
• Interphase is the period between cell
divisions. Depending on the kind of cell,
the interphase might be shorter or longer.
• The three stages or phases of the
eukaryotic interphase are G1, S, and G2.
• The M phase of the cell cycle is when
eukaryotic cells divide. Mitosis and
cytokinesis are the two stages that make
up the M phase.

5. What happens during each phase of
eukaryotic interphase?
•G1: Cells do most of their growing
during this phase. It begins when
mitosis is complete and ends
when DNA replication begins.
•S: DNA is synthesized as
chromosomes are replicated.
•G2: Many of the molecules and
cell structures required for cell
division are produced; usually the
shortest phase of the cell cycle. During interphase,
the cell grows and
replicates its DNA.

6. What happens during the M phase of
the eukaryotic cell cycle?
• The M phase is usually much shorter than
interphase and results in two daughter cells.
• The first step of the M phase is mitosis.The
cell’s nucleus divides during mitosis.
• The second step of the M phase is
cytokinesis, during which the cell’s cytoplasm
is divided.

7. What are the steps of
mitosis?
• Mitosis consists of four steps: prophase, metaphase,
anaphase, and telophase.
• Prophase: nuclear envelope breaks down, DNA
condenses, spindle begins to form.
• Metaphase: replicated chromosomes, which appear
as paired sister chromatids, line up across the center
of the cell and attach to spindle.

8. What are the steps of
mitosis?
•Anaphase: sister
chromatids separate
and move toward
ends of the cell.
•Telophase:
chromosomes
disperse, nuclear
envelope reforms.

9. What completes the M phase
of the cell cycle?
•Cytokinesis completes the M
phase of the cell cycle. It may
begin while telophase is still
taking place.
•During cytokinesis, the cytoplasm
(which includes all of the contents
of a eukaryotic cell outside the
nucleus) draws inward, eventually
pinching off into two nearly equal
parts. Each part contains a
nucleus.
(contd.)

10. What completes the M phase
of the cell cycle?
•In plant cells and other eukaryotic
cells that have a cell wall, a cell plate
forms halfway between the divided
nuclei. It gradually develops into cell
membranes and forms a complete
cell wall surrounding each daughter
cell.
•Upon the completion of cytokinesis
and the M phase, a cell enters
interphase.

11. When does DNA replicate?
•Before a cell divides in the M
phase, its DNA is duplicated by
a process called DNA
replication.
•DNA replication occurs at the
beginning of the S phase of
interphase.
•It ensures that each daughter
cell that results from cell
division will have a complete
set of DNA molecules.
6. Review Why does DNA replicate
before cell division?

12. How is the cell cycle controlled?
•Movement through the cell cycle is
subject to control by internal and
external regulators.
•Internal regulators ensure that a
cell does not move from one phase
to another until certain events
have taken place.
•External regulators respond to
events outside the cell and direct
cells to either speed up or slow
down the cell cycle.
8. Infer A set of regulatory
proteins prevents a cell from
entering anaphase until all of its
chromosomes are attached to
the mitotic spindle. Are these
regulatory proteins internal
regulators or external
regulators?

13. Progression of the cell cycle is regulated by feedback from
intracellular events

14. • Cyclin-Dependent Protein Kinase (Cdks)
A Cdks is an enzyme that adds negatively charged phosphate groups to other
molecules in a process called phosphorylation.
Through phosphorylation, Cdks signal the cell that it is ready to pass into the next
stage of the cell cycle. Cyclin-Dependent Protein Kinases are dependent on cyclins,
another class of regulatory proteins. Cyclins bind to Cdks, activating the Cdks to
phosphorylate other molecules.

15. Cyclins are named such because they undergo a constant cycle of synthesis
and degradation during cell division.
When cyclins are synthesized, they act as an activating protein and bind to
Cdks forming a cyclin-Cdk complex.
This complex then acts as a signal to the cell to pass to the next cell cycle
phase. Eventually, the cyclin degrades, deactivating the Cdk, thus signaling
exit from a particular phase.

16. Checkpoints ensure the cell cycle proceeds
without errors

18. Checkpoint: spindle assembly
•Mitosis must not complete unless all the
chromosomes are attached to the mitotic
spindle
•Mitotic checkpoint delays metaphase to
anaphase transition until all chromosomes
are attached
•Prolonged activation of the checkpoint --
>cell death
•Mechanism of many anti-cancer drugs

19. • Three Cdk4/6 inhibitors - palbociclib, ribociclib, and abemaciclib -
currently received FDA approval for clinical use to treat advanced-
stage or metastatic, hormone-receptor-positive (HR-positive,
HR+), HER2-negative (HER2-) breast cancer.

20. Mechanism of cell cycle regulation molecules revealed
•The anaphase-promoting complex/cyclosome (APC/C)
regulates cell division by marking proteins within cells for
destruction.
•Cancer is a disease of cell proliferation, A series of checks
and controls regulate each stage of this complex process,
but in cancer these 'brakes' become faulty.
•The APC/C is one of those cell cycle controls. By marking a
set of proteins for destruction, it releases the brakes and
allows cell division to proceed.

21. •APC/C marks proteins for destruction by 'tagging' them
with'ubiquitin'.These tags are recognized by proteasomes,
which are then responsible for breaking down the marked
proteins.
•The role of the APC/C is to ensure that the correct proteins
are destroyed at the right time in the cell cycle, and it does
this by ‘ubiquitinating' proteins — marking them with
ubiquitin. But how do APC/Cs know which proteins to mark?
•"Proteins contain regions known as 'degrons', destruction
boxes (D boxes) and KEN boxes,The APC/C can then bind to
these degrons using adaptors known as 'coactivators',
enabling ubiquitination of the proteins.“

22. • Function of APC/C in the cell cycle During the early stages of mitosis, APC/C–Cdc20 ubiquitinates
several substrates such as Nek2A, cyclin A and p21Cip1, promoting their degradation. Yet, in response to unattached kinetochores, the SAC is active and the APC/C is
inhibited by sequestering of Cdc20 or non-functional APC/C–Cdc20 complexes also containing Mad2, Mad3 and BubR1. Under these conditions, securin and cyclin B–Cdk1
function as inhibitors of separase. Once all chromosomes are bi-orientated on a metaphase plate, the SAC is extinguished, resulting in APC/C–Cdc20 activation. APC/C–
Cdc20 targets cyclin B1 and securin for degradation, allowing separase activity, which cleaves the centromere cohesin complex leading to anaphase onset. In yeast,
separase activation leads to dephosphorylation of Cdh1 although this pathway is not well established in mammals (question mark). The newly formed APC/C–Cdh1
complexes drive mitotic exit by targeting for destruction Plk1, Aurora A or Tpx2 among other substrates as well as Cdc20 itself. During G1 phase, APC/C–Cdh1 maintains
low levels of Cdk activity by targeting A- and B-type cyclins, among other Cdk regulators. In addition, APC/C–Cdh1 targets several regulators of DNA replication such as
Geminin or Cdc6. After the degradation of its substrates in G1, the APC catalyses the auto-ubiquitination of its own E2 ubiquitin-conjugating enzyme UBE2C/UbcH10,
leading to the stabilization of cyclin A, activation of Cdks and APC/C–Cdh1 inactivation.