Topic 4 Mitosis

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The Behavior of Chromosomes

During Mitosis
Phạm Phước Thành, MD
30/09/2024
Introduction to Mitosis
• - Overview of Cell Division: Introduce cell
division as a fundamental process in growth,
development, and tissue repair.
• - Importance of Mitosis in Cellular Functions:
Highlight how mitosis ensures genetic
consistency across cells, supporting
organismal functions.
Systems of Cell Reproduction
Unicellular organisms use cell division primarily to reproduce themselves,
whereas in multicellular organisms cell division also plays important roles in
growth and in the repair of tissues. In order for any cell to divide, four events
must occur:
- There must be a reproductive signal. This signal, which may come either
from inside or outside the cell, initiates the cellular reproductive events.
- Replication of DNA (the genetic material) and other vital cell components
must occur so that each of the two new cells will be identical and have
complete cell functions.
- The cell must distribute the replicated DNA to each of the two new cells. This
process is called segregation.
- New material must be added to the cell membrane (and the cell wall, in
organisms that have one) in order to separate the two new cells in a process
called cytokinesis.

These four events occur in prokaryotes in different ways than eukaryotes.


In prokaryotes, cell division
results in the reproduction of the
entire single-celled organism.
The cell grows in size,

Prokaryotes replicates its DNA, and then


essentially divides into two new
divide by cells, a process called fission.
fission
• REPRODUCTIVE
SIGNALS.
• REPLICATION OF DNA.
• SEGREGATION OF DNA.
• CYTOKINESIS.
Eukaryotic cells divide by mitosis or
meiosis
• Complex eukaryotes, such as humans and flowering plants, originate from a single cell, the fertilized egg. This cell derives
from the union of two sex cells, called gametes, from the organism’s parents—that is, a sperm and egg—and so contains
genetic material from both of these parental cells. This means that the fertilized egg contains one set of chromosomes from the
male parent and one set from the female parent.
• The formation of a multicellular organism from a fertilized egg is called development.
- Eukaryotic cells do not constantly divide whenever environmental conditions are adequate. In fact, eukaryotic cells that are
part of a multicellular organism and have become specialized seldom divide. So the signals for cell division are related not to
the environment of a single cell, but to the needs of the entire organism.
- Instead of a single chromosome, eukaryotes usually have many (humans have 46), so the processes of replication and
segregation, while basically the same as in prokaryotes, are more intricate.
- Eukaryotic cells have a distinct nucleus, which has to be replicated and then divided into two new nuclei. Thus, in eukaryotes,
cytokinesis is distinct from division of the genetic material.
- Cytokinesis is different in plant cells (which have a cell wall) than in animal cells (which do not).
• The key difference between prokaryotic and eukaryotic cell reproduction is that in the eukaryotes, newly replicated
chromosomes remain associated with each other as sister chromatids, and a new mechanism, mitosis, is used to segregate
them into the two new nuclei.
• A second mechanism of nuclear division, meiosis, occurs in germ cells that produce gametes that contribute to the
reproduction of a new organism. While the two products of mitosis are genetically identical to the cell that produced them—
they both have the same DNA—the products of meiosis are not. Meiosis generates diversity by shuffling the genetic material,
resulting in new gene combinations. It plays a key role in sexual life cycles.
Phases of the Cell Cycle
• Interphase: Preparation for Mitosis: the
stages of interphase (G1, S, G2) and the
preparation of the cell for mitosis.

• The Mitotic Phase: Division of the Nucleus:


How the cell enters the mitotic phase, and the
events leading to the division of the nucleus.
Interphase and
the Control of Cell Division
• A cell lives and functions until it divides or dies. Or, if it is a gamete, it lives until it
fuses with another gamete.
• What cells lose the capacity to divide as they mature? RBC, Muscle cells, nerve
cells.
• What cells divide rarely? cortical cells in plant stems
• What cells divide rapidly? Embryo, cancer.
• Between divisions—that is, for most of its life—a eukaryotic cell is in a condition
called interphase. For most types of cells, we may speak of a cell cycle that has two
phases: mitosis and interphase. even in tissues engaged in rapid growth, cells spend
most of their time in interphase.
Cells prepare for
mitosis:
2 identical
chromatids and
components of
microtubules.
G1 length differs from
cell types.
Each chromosome is
single, unreplicated.
Cyclin-dependent kinase: Cdk

Cyclins and
other
proteins
signal
events in
the cell
cycle
- Cyclin D-Cdk4 acts during the middle of G1.
This is the restriction point (R), a key
decision point beyond which the rest of the
cell cycle is normally inevitable.
- Cyclin E-Cdk2 also acts in the middle of G1.
- Cyclin A-Cdk2 acts during S, and also
stimulates DNA replication.
- Cyclin B-Cdk1 acts at the G2–M boundary,
initiating the transition to mitosis.
Growth factors can stimulate cells to divide

• Growth factors: external signals (chemical


messengers) stimulate cells to divide.
• Ex: Platelet-derived GF
• Interleukins
• EPO.
Eukaryotic Chromosomes
• Human & other eukaryotes have > 1
chromosome (CSO).
• Component: Chromatin: Linear, double-
stranded DNA + proteins.
• Before S phase: 1 CSO with 2-strand DNA
• During replication-S phase: 1 CSO = 2 CMD
Chromosomes have a hierarchic organization

Life The Science of Biology, 7th Edition


Mitotic chromosomes are formed from chromatin in its most
condensed form
Mitosis: Distributing Exact Copies
of Genetic Information
Mitotic Stages (part 1)

Interphase: The
centrosomes determine
the plane of cell
division.

Prophase: Chromatids
become visible and the
spindle forms during
prophase
cohesin
Mitotic Stages (part 2)

• Metaphase: alignment of chromosomes at the metaphase plate, securin bound to and inhibits
separatase; hydrolysis of securin -> activation.
• Anaphase: separation of sister chromatids and the movement towards opposite poles, driven
by spindle microtubules:
- cytoplasmic dynein, hydrolyzes ATP -> ADP PO4, thus releasing energy to move the CSO
along the microtubules toward the poles. These motor proteins account for about 75% of the
force of motion.
- The kinetochore microtubules shorten from the poles, drawing the CSO toward them. This
shortening accounts for about 25% of the motion.
• Telophase: Cover the reformation of the nuclear envelope around the separated chromatids
and the final division of the cytoplasm during cytokinesis.
- Two daughter CSO, containing identical DNA and carrying identical sets of hereditary
instructions, are now at the opposite ends of the spindle, which begins to break down.
- The CSO begin to uncoil, continuing until they become the diffuse tangle of chromatin that is
characteristic of interphase.
- The nuclear envelopes and nucleoli, coalesce and reform their respective structures.
Cytokinesis: The Division of the Cytoplasm
The invisible thread is actually Following cytokinesis, both daughter cells contain all
microfilaments of actin and myosin the components of a complete cell.
located in a ring just beneath the A precise distribution of chromosomes is ensured by
plasma membrane. These two mitosis.
proteins interact to produce a Organelles: ribosomes, mitochondria, & chloroplasts
contraction, just as they do in need not be distributed equally between daughter
muscles, thus pinching the cell in cells.
two. There is no mechanism with a precision comparable to
that of mitosis to provide for their equal allocation to
daughter cells.
Clinical Relevance of Mitosis
1. Cancer
Uncontrolled Cell Division: Cancer is primarily caused by mutations in genes that regulate mitosis.
When these genes are damaged, cells divide uncontrollably, leading to tumor formation.
Therapeutic Target: Many cancer treatments, including chemotherapy (e.g., taxanes and vinca
alkaloids) and radiation therapy, aim to disrupt mitosis. These therapies prevent cancer cells from
dividing by targeting components like microtubules or DNA replication mechanisms.
2. Tissue Regeneration and Healing
- Wound Healing: Mitosis is essential for the replacement and repair of damaged cells. In wound
healing, mitotic activity increases to replace dead or damaged tissue, allowing for recovery.
- Stem Cell Therapy: Mitosis is also crucial in regenerative medicine, where stem cells divide and
differentiate to repair tissues, such as in heart disease, bone injuries, or neurodegenerative
conditions.
3. Developmental Disorders
- Congenital Anomalies: Errors in mitosis during fetal development can result in congenital
abnormalities, including chromosomal disorders like Down syndrome (trisomy 21), where
improper chromosome segregation occurs during mitosis.
- Growth Deficiencies: Problems with mitotic regulation can lead to developmental delays or
growth disorders.
4. Aging
- Cellular Senescence: Over time, the ability of cells to undergo mitosis diminishes,
contributing to aging. Telomere shortening during cell division limits the number of
times a cell can divide, which can lead to tissue degeneration.
- Cancer and Aging: The decline in mitotic efficiency with age also leads to increased
susceptibility to cancer, as aged cells accumulate mutations that affect mitosis.
5. Genetic Disorders
- Chromosomal Instabilities: Errors during mitosis, such as nondisjunction (failure of
chromosomes to separate properly), can result in aneuploidy (abnormal number of
chromosomes), contributing to genetic diseases.

6. Reproductive Health
- Fertility: Proper mitotic division is essential in the formation of gametes (eggs and
sperm) during meiosis. Defects in mitotic checkpoints can lead to infertility or
miscarriage.
Thank you

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