Cell Growth and Division: The Cell Cycle

Cell growth and division:
the cell cycle
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
CELL CYCLE
The cell cycle is regulated by a molecular control

system
• The frequency of cell division varies with the type

of cell and with cell “happiness”
• These cell cycle differences result from regulation
at the molecular level
• The cell cycle appears to be driven by specific
chemical signals present in the cytoplasm
• The levels of these chemical signals are
influenced by biotic & abiotic factors
1
• Some eukaryotic cell-cycle times
The eukaryotic cell cycle is divided into four phases
2
A central control system triggers the major
processes of the cell cycle
Trigger completion
Trigger mitosis
of mitosis and
machinery
proceed to cytokinesis
Trigger DNA replication

machinery
The cell-cycle control system

There are two main key classes of regulatory molecules
that determine the cell cycle progression:
• the cyclins
• and cyclin-dependent
kinases (Cdks)
http://jpkc.scu.edu.cn
3
The cell cycle control system depend on

cyclically activated protein kinases
Cyclin-dependent kinases (Cdks)
• Cyclin-dependent kinases (CDKs) are a family of protein kinases first
discovered for their role in regulating the cell cycle
• The activity of each of these kinases rises and falls in a cyclical
fashion
• Activation/inactivation of these Cdk-complexes regulate the cell cycle
4
Cyclins:
• Cyclins are a family of proteins that control the progression
of cells through the cell cycle by activating cyclin-dependent
kinase (Cdk) enzymes.
• Cyclins are so named because their concentration varies in
a cyclical fashion during the cell cycle
• Cyclin-dependent kinases are regulated by the

accumulation and destruction of cyclins
M-cyclin: the cyclin that helps drive cells into M phase is called M-cyclin.
M-cyclins are ubiquitinated by APC (anaphase promoting complex)
5
• The activity of Cdks are also regulated by phosphorylation
and dephosphorylation
• Different Cyclin-Cdk complexes trigger different steps in

the cell cycle
G
0
Cyclin
B&
Cdc 2 Cyclin D
& Cdk
Cyclin E 4/6
& Cdk 2
Cyclin A & Cdk 2

6
• Cdks are
inactivate through
most of G1
Inactive
Cdk
Inactive
Cdk
7
M-Cdk triggers mitosis machinery
chromosome condensation, nuclear envelope

breakdown, actin cytoskeleton rearrangement
S-Cdk triggers DNA replication and ensures that

DNA replication is initiated only once per cell cycle
8
The cell cycle checkpoints
G1 checkpoint
M checkpoint
G2 checkpoint
• The sequential events of the cell cycle are directed by a

distinct cell cycle control system, which is similar to a clock
• The clock has specific checkpoints where the cell cycle
stops until a go-ahead signal is received
• For many cells, the G1 checkpoint seems to be the most
important one
Cell cycle checkpoints allowing cells to monitor its internal

state and its environment before continuing through the
cycle
9
DNA damage arrests the cell cycle in G1
10
Mitotic spindle checkpoint is off only when all chromosomes are
attached appropriately to the mitotic spindle. And the APC is then
activated …
The cell cycle control system can arrest the cycle at

various checkpoints
11
Cell can dismantle their control system and
withdraw from the cell cycle…
Apoptosis
12
Programmed Cell Death (Apoptosis)
• Apoptosis is regulated by members of the Bcl-2 family of

intracellular proteins
• Apoptosis is carried out by a family of proteases –

enzymes that cut up other protein – called caspases.
13
• Apoptosis is carried out by a family of proteases –
enzymes that cut up other protein – called caspases.
Extracellular control of cell numbers and cell size
Animal cells
require
extracellular
signals to Divide
Mitogens Growth factors Survival factors
14
Mitogens stimulate cell division
Extracellular growth factors stimulate cells to

growth
15
Extracellular growth factors stimulate cells to
growth
Cells size is controlled

in animals
Different
cell types
grow to be
so different
in size
Animal cells require survival factors to avoid

apoptosis
16
Some extracellular signal proteins inhibit cell
growth, division or survival
Mutation of myostatin gene leads to a dramatic increase in muscle mass
Cell division
Overview: The Key Roles of Cell Division
• The ability of organisms to reproduce best

distinguishes living things from non-living matter
• The continuity of life is based upon the
reproduction of cells, or cell division
• Cell division is integral part of cell cycle
17
Types of cell division
• Prokaryotes
– Binary fission
• Eukaryotes
– Mitosis:
• Growth, development & repair
• Asexual reproduction (yields genetically identical cells)
• Occurs in somatic (body) cells
– Meiosis:
• Sexual reproduction (yields genetically different cells with half
the # of chromosomes)
• Occurs in specific reproductive cells
• Yields gametes (e.g., eggs & sperm) or spores
• Eukaryotic cell division consists of:

– Mitosis, the division of the nucleus
– Cytokinesis, the division of the cytoplasm
18
Mitotic cell division results in genetically identical
daughter cells
• Cells duplicate their genetic material before they divide,

ensuring that each daughter cell receives an exact copy of
the genetic material, DNA
• A dividing cell duplicates its DNA, allocates the two copies
to opposite ends of the cell, and only then splits into
daughter cells
Overview of M phase
• In preparation for the M phase, DNA-binding

proteins configure replicated chromosomes for
segregation
19
Distribution of Chromosomes During Cell Division
• In preparation for cell 0.5 µm
division, DNA is replicated

and the chromosomes
Chromosome
condense duplication
(including DNA
synthesis)
• Each duplicated Centromere
chromosome has two sister

chromatids, which separate
during cell division Sister
chromatids
• The centromere is the Separation
narrow “waist” of the of sister

chromatids
duplicated chromosome,
where the two chromatids
are most closely attached Centromeres Sister chromatids
Mitotic phase
• Mitosis is conventionally divided into five phases:
– Prophase
– Prometaphase
– Metaphase
– Anaphase
– Telophase
• Cytokinesis is well underway by late telophase
20
21
Mitotic phase
Microtubule instability facilitates the

formation of the mitotic spindle
Mitotic phase
The Mitotic Spindle is Responsible for

Chromosome Movements During Mitosis
22
Mitotic phase
The cytoskeleton carries out both mitosis

and cytokinesis
Mitotic phase
1. Prophase: The Mitotic Spindle Start to Assemble
- Chromatin condenses, this causes the chromosomes to

begin to become visible
- Centrosomes separate, moving to opposite ends of the

nucleus
- The centrosomes start to form a framework used to

separate the two sister chromatids called the mitotic
spindle, that is made of microtubules
- Nucleolus disappears
23
• The centrosome functions as
a microtubule-organizing center
(MTOC) where microtubules are
assembled and anchored
• As they move apart, each

centrosome acts as a nucleation
sits for microtubule assembly
and the region between the two
centrosome begins to fill with
microtubules destined to form
the mitotic spindle
The Mitotic Spindle Start to Assemble

A bipolar mitotic spindle is formed by the
selective stabilization of interacting
microtubules:
-New microtubules grow out in random
directions from the two centrosomes.
- The minus ends anchore in the

centrosome
- The free plus ends are dynamically

unstable and swithch suddenly from uniform
growth (outward-pointing red arrows) to
rapid shrinkage (inward-pointing red arrows)
- The cross-link the microtubules together

(black dots) stabilizes their plus ends by
decreasing the probability of their
depolymeration
24
Mitotic phase
2. Prometaphase: Chromosomes attach to the mitotic spindle
- Nuclear envelope fragments
- Chromosomes become more condensed
- A kinetochore is formed at the centromere, the point where

the sister chromatids are attached
- Microtubules attach at the kinetochores
Three types of spindle microtubules: kinetochore microtubules;

polar microtubules and aster microtubules
25
Mitotic phase
3. Metaphase: Chromosomes Line Up at the Spindle Equator
Aster
- Chromosomes align at the Sister
Centrosome
quarter of the spindle , chromatids

Metaphase
plate
forming the metaphase plate
Kineto-
chores
- Note: the spindle consists
of microtubules, one
attached to each
chromosome
Overlapping
nonkinetochore Kinetochore
microtubules microtubules
0.5 µm
•Two different kinds of forces, pulling and pushing, drive

chromosomes to alignment at the metaphase plate
•Chromosomes at the metaphase plate are held there
under considerable tension
26
Mitotic phase
4. Anaphase: Daughter chromosomes segregate
- The cohesin linkage between sister chromatids is

released, each centromere splits making two chromatids
free
- Each chromatid moves toward a spindle pole to which it

attached.
- The movement of the chromosomes is the consequence

of two independent processes called anaphase A and
anaphase B
- Cell begins to elongate, caused by microtubules not

associated with the kinetochore
-
Mitosis involves at least three separate groups of motor proteins, operating at

the plus end of kinetochore microtubules, polar microtubules and astral
microtubules
27
Mitotic phase
5. Telophase: The Nuclear Envelope Re-form
• Formation of nuclear membrane and nucleolus
• Short and thick chromosomes begin to elongate to form

long and thin chromatin
• Formation of the cleavage furrow - a shallow groove in

the cell near the old metaphase plate
• Cytokinesis = division of the cytoplasm
28
Mitotic phase
6. Cytokinesis: the cleavage of cytoplasm
• In animal cells, cytokinesis occurs by a process known as
cleavage, forming a cleavage furrow. This process involves in a
transient structure based on actin and mysin filaments – the
contractile ring
• In plant cells, a cell plate forms during cytokinesis
Cleavage furrow
Daughter cells
Contractile ring of
microfilaments
• The mitotic spindle determines the plane of

cytoplasmic cleavage
29
• Contractile ring of animal cells is made of actin and
myosin
The Mitotic Spindle: A Closer Look
• The mitotic spindle is an apparatus of microtubules that

controls chromosome movement during mitosis
• Assembly of spindle microtubules begins in the
centrosome, the microtubule organizing center (MTOC)
• The centrosome replicates, forming two centrosomes that
migrate to opposite ends of the cell, as spindle
microtubules grow out from them
• A radial array of short microtubules extends from each
centrosome
• The spindle includes the centrosomes, the spindle
microtubules, and the asters
30
• Some spindle microtubules attach to the kinetochores of
chromosomes and move the chromosomes to the
metaphase plate
• In anaphase, sister chromatids separate and move along
the kinetochore microtubules toward opposite ends of the
cell
• The microtubules shorten by depolymerizing at their
kinetochore ends
• Nonkinetochore microtubules from opposite poles overlap
and push against each other, elongating the cell
• In telophase, genetically identical daughter nuclei form at
opposite ends of the cell
31

Cell Growth and Division: The Cell Cycle

Enviado por

Dados do documento

Título original

Direitos autorais

Formatos disponíveis

Compartilhar este documento

Compartilhar ou incorporar documento

Opções de compartilhamento

Você considera este documento útil?

Este conteúdo é inapropriado?

Direitos autorais:

Formatos disponíveis

Cell Growth and Division: The Cell Cycle

Enviado por

Direitos autorais:

Formatos disponíveis

Cell growth and division:

the cell cycle

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

The cell cycle is regulated by a molecular control

• The frequency of cell division varies with the type

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

The eukaryotic cell cycle is divided into four phases

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Trigger DNA replication

The cell-cycle control system

The cell cycle control system depend on

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

The cell-cycle control system

• Cyclin-dependent kinases are regulated by the

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

The cell-cycle control system

• Different Cyclin-Cdk complexes trigger different steps in

Cyclin A & Cdk 2

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

The cell-cycle control system

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

chromosome condensation, nuclear envelope

S-Cdk triggers DNA replication and ensures that

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

The cell cycle checkpoints

• The sequential events of the cell cycle are directed by a

Cell cycle checkpoints allowing cells to monitor its internal

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

DNA damage arrests the cell cycle in G1

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

The cell cycle control system can arrest the cycle at

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

• Apoptosis is regulated by members of the Bcl-2 family of

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

• Apoptosis is carried out by a family of proteases –

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Extracellular control of cell numbers and cell size

Mitogens Growth factors Survival factors

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Extracellular growth factors stimulate cells to

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Cells size is controlled

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Animal cells require survival factors to avoid

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Mutation of myostatin gene leads to a dramatic increase in muscle mass

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Overview: The Key Roles of Cell Division

• The ability of organisms to reproduce best

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

• Eukaryotic cell division consists of:

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

• Cells duplicate their genetic material before they divide,

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

• In preparation for the M phase, DNA-binding