GUIDED BY: PRESENTED BY:

DR.JYOTI BHOJWANI AVNISH MISHRA

FACULTY, GENETICS
DAVV, INDORE
Cell Cycle
 A cell’s life is called the “cell
cycle”.
– Part 1: Interphase

– Part 2: Cell Division (broken

into at least 5 steps)
Cell Cycle
The cell cycle.
Two Forms of Cell Division:
Defined
 Mitosis
– “The division of a single nucleus into
two genetically identical “daughter
cells” (clones).”
 Meiosis
– “In a sexually reproducing organism,
the division of a single diploid
nucleus into four haploid daughter
cells (gametes or sex cells).”
 Mitosis: A general overview
 The division of somatic cells
follows a “2-D” process: Duplicate
& Divide Daughter Cell

Parent Cell 46
Chromosomes
46 92
Chromosomes Chromosomes (Divide)
Daughter Cell
(Duplicate)
46
Chromosomes

Start End
 Meiosis: A general overview
 The division of sex cells follows a
“3-D” process: Duplicate, Divide &
Divide

46 23
Chromosomes Chromosomes

23
46 92 (Divide)
Chromosomes
Chromosomes (Divide)
Chromosomes
(Duplicate)
46 23
Chromosomes Chromosomes

23
Chromosomes
Mitosis: A closer look
 The short process of Mitosis takes
place in five steps:
– Prophase
– Metaphase
– Anaphase
– Telophase
– Cytokinesis (“Cell-splitting”)
Prophase The
Stages of
Mitosis
Interphase
Metaphase

Anaphase Telophase
 The Spindle
A spindle is a web type structure made
up of microtubule fibres. It is essential
for mitosis because it arranges the
chromosomes into their correct positions
in preparation for cell division.
Mitotic centre

A cell at metaphase a spindle

Microtubule
Chromosomes attached to
spindle during nuclear division
 Interphase begins

Cell Cycle
Interphase ends
 INTERPHASE
After a cell has divided, the two
new cells begin the process again,
the cells at this stage are in
Interphase.

It is divided into three mini stages:- G1

S
Cell cycle G2
Eukaryotic chromsome replicating
 1. Prophase
Cell Cycle
PROPHASE
 The chromatin (unravelled DNA) in
the nucleus, condenses to form
pairs of chromosomes.
• As this is happening the nucleolus
begins to break down

• The centrioles move to opposite

ends of the nucleus.
• Nuclear membrane begins to break down
PROPHASE
 Chromatin
condenses
(remember that
chromatin/DNA
replicate during
Interphase), the
nuclear envelope
dissolves,
centrioles (if
present) divide and
migrate, the spindle
forms.
Cell Cycle 2. Metaphase
 METAPHASE
 The spindle becomes
fully developed

• The chromatid pairs

place themselves
onto individual fibres
and are aligned along
the centre of the
spindle

• The nuclear membrane has completely gone

Cell Cycle 3. Anaphase
ANAPHASE
 The chromatid pairs are
split into two
(This is done by
movement of the spindle
fibres)
 The pairs then travel to
opposite ends of the
spindle
 The halved chromatids
are now called
chromosomes
Cell Cycle
4. Telophase
 TELOPHASE
Two new nuclei are formed when
the chromosomes reach the
opposite poles of the cell
The nuclear membrane is formed- the nucleolus
reappears
The chromosomes disperse in the nucleus
 Cytokinesis(site-o-kin-ee-sis)
 Key activities:
The cell completely splits in
two.
Presto change-o! You have two
identical cells!
 CYTOKINESIS
Literally means, division of the
cytoplasm

Mitosis is the splitting of the nucleus.

Cytokinesis is the splitting of cytoplasm

It usually begins during ANAPHASE

© 2003 John Wiley and Sons Publishers
Organs which need to produce
new cells continuously have
the highest turnover.(eg. stem
cell producing organs/organ
systems)

For example:-

Bone marrow-
producing replacement
blood cells
The testes - producing
semen
(1000 spermatogonial cells/heartbeat)
Cells
 Overview of Cell Cycle There’s no
turning back,
now!
Control
 Two irreversible points in cell cycle
– replication of genetic material
– separation of sister chromatids
 Checkpoints
– process is assessed & possibly halted
sister chromatids

centromere  
single-stranded double-stranded
chromosomes chromosomes
 Checkpoint control system
Checkpoints are locations in the cell
cycle where a cell will be stopped so
that it can be checked for mistakes.
Hey buddy, I don’t
care whatcha say! I
am not letting you
through unless your
DNA is correct!
Checkpoint control system
– cell cycle controlled by STOP & GO
chemical signals at critical points
– signals indicate if key cellular
processes have been
completed correctly
 Checkpoint control system
 3 major checkpoints:
– G1/S
• can DNA synthesis begin?
– G2/M
• has DNA synthesis been
completed correctly?
• commitment to mitosis
– spindle checkpoint
• are all chromosomes
attached to spindle?
• can sister chromatids
separate correctly?
G1/S checkpoint
 G1/S checkpoint is most critical
– primary decision point
• “restriction point”
– if cell receives “GO” signal, it replicates
• internal signals: cell growth (size), cell nutrition
• external signals: “growth factors”
– if cell does not receive
signal, it exits cycle &
switches to G0 phase
• non-dividing, working state
 G0 phase
 G0 phase
– non-dividing, differentiated state
– most human cells in G0 phase
M
 liver cells
Mitosis
 in G0, but can be
G2
Gap 2 “called back” to cell
G1
Gap 1 cycle by external cues
 nerve & muscle cells
G0
S Resting  highly specialized
Synthesis
 arrested in G0 & can
never divide
Activation of cell division

 How do cells know when to

divide?
– cell communication signals
• chemical signals in cytoplasm give cue
• signals usually mean proteins
Activators, Inhibitors

experimental evidence: Can you explain this?

“Go-ahead” signals
 Protein signals that promote cell growth
& division
– internal signals
• “promoting factors”
– external signals
• “growth factors”
 Primary mechanism of control
– phosphorylation
• kinase enzymes
• either activates or inactivates cell signals
 Cell cycle signals inactivated Cdk

 Cell cycle controls

– cyclins
• regulatory proteins
• levels cycle in the cell
– Cdk’s
activated Cdk
• cyclin-dependent kinases
• phosphorylates cellular proteins
– activates or inactivates proteins
– Cdk-cyclin complex
• triggers passage through different stages of
cell cycle
 Spindle checkpoint
G2 / M checkpoint
Chromosomes attached
• Replication completed at metaphase plate
• DNA integrity
Inactive
Active Active
Inactive Cdk / G2 M APC cytokinesis
cyclin (MPF) C
G2 mitosis

G1

S Cdk / G1
cyclin
Inactive
MPF = Mitosis Active
Promoting Factor G1 / S checkpoint • Growth factors
APC = Anaphase • Nutritional state of cell
Promoting Complex • Size of cell
 Cyclin & Cyclin-dependent
kinases
 CDKs & cyclin drive cell from
one phase to next in cell cycle
 proper regulation of cell
cycle is the key to life:
and the genes for these
regulatory proteins
have been highly
conserved through
evolution
 the genes are basically

the same in yeast,

insects, plants &
animals (including
humans)
1. A Cascade of Protein
Phosphorylations
Phosphorylation = phosphate groups (PO4) are
added onto substrates by enzymes called kinases

That guy Kinase asked me

out and then told me he Oh no
wanted give me a he
phosphate group to turn
me on…ugh..men!
didn’t
.
 Growth Factors and Cancer
 Growth factors can create cancers
– proto-oncogenes
• normal growth factor genes that become
oncogenes (cancer-causing) when mutated
• stimulates cell growth
• if switched “ON” can cause cancer
• example: RAS (activates cyclins)
– tumor-suppressor genes
• inhibits cell division
• if switched “OFF” can cause cancer
• example: p53
 Cancer & Cell Growth
 Cancer is essentially a failure
of cell division control
– unrestrained, uncontrolled cell growth
 What control is lost?
– lose checkpoint stops
– gene p53 plays a key role in G1/S restriction point
• p53 protein halts cell division if it detects damaged
p53 is the
DNA
– options:
Cell Cycle
• stimulates repair enzymes to fix DNA
Enforcer
• forces cell into G0 resting stage
• keeps cell in G1 arrest
• causes apoptosis of damaged cell
• ALL cancers have to shut down p53 activity

p53 discovered at Stony Brook by Dr. Arnold Levine

 NORMAL p53
p53 — master regulator
gene p53 allows cells
with repaired
DNA to divide.
p53
protein DNA repair enzyme
p53
protein

Step 1 Step 2 Step 3

DNA damage is caused Cell division stops, and p53 triggers the destruction
by heat, radiation, or p53 triggers enzymes to of cells damaged beyond
chemicals. repair damaged region. repair.

ABNORMAL p53

abnormal
p53 protein

cancer
Step 1 Step 2 cell
DNA damage is The p53 protein fails to stop Step 3
caused by heat, cell division and repair DNA. Damaged cells continue to divide.
radiation, or Cell divides without repair to If other damage accumulates, the
chemicals. damaged DNA. cell can turn cancerous.
 Development of Cancer
 Cancer develops only after a cell
experiences ~6 key mutations (“hits”)
– unlimited growth
• turn on growth promoter genes
– ignore checkpoints
• turn off tumor suppressor genes (p53)
– escape apoptosis
• turn off suicide genes
It’s like an
– immortality = unlimited divisions out of control
• turn on chromosome maintenance genes car!
– promotes blood vessel growth
• turn on blood vessel growth genes
– overcome anchor & density dependence
• turn off touch-sensor gene
Regulation of cell cycle
 cyclins and cyclin-dependent kinases
(CDKs), determine a cell's progress
through the cell cycle
 Leland H. Hartwell, R. Timothy Hunt,
and Paul M. Nurse won the 2001 Nobel
Prize in Physiology or Medicine for their
discovery of these central molecules
 relevant genes were first identified by
studying yeast, especially
Saccharomyces cerevisiae
 Frequency of cell division
 Frequency of cell division varies by cell
type
– embryo
• cell cycle < 20 minute
– skin cells
• divide frequently throughout life
• 12-24 hours cycle
– liver cells M
metaphase anaphase
prophase telophase
• retain ability to divide, but keep it in reserve C
• divide once every year or two G 2

– mature nerve cells & muscle cells interphase (G1, S, G2 phases)

mitosis (M)
• do not divide at all after maturity S
cytokinesis (C) G1

• permanently in G0
Traditional treatments for
cancers
 Treatments target rapidly dividing cells
– high-energy radiation
• kills rapidly dividing cells
– chemotherapy
• stop DNA replication
• stop mitosis & cytokinesis
• stop blood vessel growth