Lecture Six… Cell Cycle and Cell Division (a)uowa.edu.iq › filestorage ›...
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Ass. Lec Ghufran S. Salih Cytology/ Second Stage
2018/ 2019 First semester
University of Warith Al-Anbiyaa College of Engineering Biomedical Engineering
Lecture Six… Cell Cycle and Cell Division (a)
1. Cell Cycle or Cell Division
Cell division is a very important process in all living organisms. During
the division of a cell, DNA replication and cell growth also take place.
All these processes, i.e., cell division, DNA replication, and cell growth,
hence, have to take place in a coordinated way to ensure correct division
and formation of progeny cells containing intact genomes. The sequence
of events by which a cell duplicates its genome, synthesizes the other
constituents of the cell and eventually divides into two daughter cells
is termed cell cycle. Although cell growth (in terms of cytoplasmic
increase) is a continuous process, DNA synthesis occurs only during one
specific stage in the cell cycle. The replicated chromosomes (DNA) are
then distributed to daughter nuclei by a complex series of events during
cell division. These events are themselves under genetic control.
Cell Lifespan
Cell pass through life at four stages
- Born
- Differentiate
- Function
- Die or Divide
Lifespan Processes
- Birth…… Mitosis (except germ cells - Meiosis)
- Growth ......Expression of genes and proteins required to grow the
cell, its organelles and cytoskeleton
- Function……Expression of tissue specific genes and proteins
- Division……DNA during cycle, whole cell in Mitosis
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Ass. Lec Ghufran S. Salih Cytology/ Second Stage
2018/ 2019 First semester
University of Warith Al-Anbiyaa College of Engineering Biomedical Engineering
- Death…….Apoptosis (programmed cell death) Necrosis (un
programmed cell death)
Cell Lifespan Examples
Intestinal epithelial cells 3–5 days
Red blood cell 120 days
Brain neuron, heart 50 - 100 years
Neutrophil in circulation 6-7 hours; in tissue 4 days
Chromosomes
A. Composition
1. Chromatin
a. DNA and protein
b. Present in non-dividing cells
c. Chromosomes condense during cell division
2. Nucleosomes
a. Part of the chromatin
b. Packaged when different types of histones interact
- Histone (H1) associates with the linker histone, Creates 30 nm diameter
fibers, Fibers form loops held together by scaffolding proteins, These
interact to form the condensed chromosome seen in metaphase
3. DNA
a. Organized into informational units called genes, Chromosomes contain
hundreds to thousands of genes , Humans have less than 30,000 genes
that code for proteins.
b. DNA in chromosomes is packaged in a highly organized way, which
associated with positively charged histone proteins and form beadlike
nucleosomes. Each nucleosome is composed of 146 base pairs wrapped
around 8 histones.
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Ass. Lec Ghufran S. Salih Cytology/ Second Stage
2018/ 2019 First semester
University of Warith Al-Anbiyaa College of Engineering Biomedical Engineering
B. Chromosomes of different species differ in number and
information content
1. Humans and several other species of organisms have 46 chromosomes
2. The number of chromosomes does not provide information about the
organism
3. chromosomes carry the genetic information of a cell to the next
generation, and to offspring
Figure 6.1: Structure of chromosome and their compositions
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Ass. Lec Ghufran S. Salih Cytology/ Second Stage
2018/ 2019 First semester
University of Warith Al-Anbiyaa College of Engineering Biomedical Engineering
2. Stages of the eukaryotic cell cycle
• The cell cycle describes the status of cells in relationship to growth and division:
1. when cells reach a certain size, growth either stops or the cell must divide
2. most, but not all, eukaryotic cells are capable of dividing
3. cell division is generally a highly regulated process
4. the generation time for eukaryotic cells varies widely, but is usually 8-20 hours
• Cell cycle includes all events from a cell’s formation until it
divides into two major periods (figure 6.2):
a. Interphase
b. Cell division (mitosis: nuclear division and cytokinesis:
cytoplasmic division).
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Ass. Lec Ghufran S. Salih Cytology/ Second Stage
2018/ 2019 First semester
University of Warith Al-Anbiyaa College of Engineering Biomedical Engineering
Figure 6.1: Stages of cell cycle
A. interphase
• Metabolic or growth phase
• From cell formation until cell division
• 90% of the cell cycle
• DNA replication
• Preparation for division
• It is divided into subphases:
1. G0: cells that do not divide become arrested in this phase, G0 can last
minutes to years.
2. S: synthetic phase; the DNA is completely replicated (genetic
information duplicated).
3. G1: growth phase with little cell division related activities
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Ass. Lec Ghufran S. Salih Cytology/ Second Stage
2018/ 2019 First semester
University of Warith Al-Anbiyaa College of Engineering Biomedical Engineering
4. G2: brief period of growth where enzymes and other proteins necessary
for division are synthesized
B. cell division has two main parts – mitosis and cytokinesis
1. mitosis is the process that distributes a complete copy of the duplicated
genetic information to each daughter cell.
2. cytokinesis is the process of dividing the cytoplasm into two separate
cells. some cells can have mitosis without cytokinesis (most common in
fungi and slime molds)
Mitotic Cell Division
A. Characteristics
1. Daughter cells (2) are identical to mother cell
2. No gain or loss of genetic material
3. Series of continuous events
4. Lasts about two hours
B. Phases of mitosis
1. Cellular characteristics at end of G2
a. Nucleus with nuclear membrane
b. Nucleoli present
c. Two centrosomes present
i. Closely affiliated with nucleus
d. Pair of centrioles present in each centrosome
e. Aster is around each centriole pair
i. Array of microtubules
f. Genetic material is still in chromatin form
2. Characteristics of Prophase
a. Nucleus
- Nucleoli disappear
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Ass. Lec Ghufran S. Salih Cytology/ Second Stage
2018/ 2019 First semester
University of Warith Al-Anbiyaa College of Engineering Biomedical Engineering
- Chromatin condenses to form chromosomes
- Each chromosome (duplicated during S phase) forms a pair of sister
chromatids
- Sister chromatids are joined at a centromere by protein tethers
- Centromeres contain a kinetochore where microtubules will bind
- Each sister chromatid has its own kinetochore
b. Cytoplasm
- A system of microtubules, called the mitotic spindle, organizes between
the two poles (opposite ends) of the cell, each pole has a microtubule
organizing center (MTOC), in animals and some other eukaryotes,
centrioles are found in the MTOC.
- Centrosomes migrate toward the poles along the nuclear surface.
- Spindles lengthen.
3. Characteristics of Prometaphase
a. Nuclear membrane disappears and spindles interact with chromosomes
b. Spindles extend from each pole toward the cell’s equator
c. Non-kinetochore microtubules radiate from the centrosomes toward the
metaphase plate, Microtubules overlap with those of the opposite pole
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Ass. Lec Ghufran S. Salih Cytology/ Second Stage
2018/ 2019 First semester
University of Warith Al-Anbiyaa College of Engineering Biomedical Engineering
Figure 6.2: Mitosis cycle (Interphase, Prophase, Prometaphase).
4. Characteristics of Metaphase
- Chromosomes line up along the mid-plane of the cell (the metaphase
plate), chromosomes are most condensed, most visible, and most
distinguishable during metaphase
- The mitotic spindle, now complete, has two types of microtubules
• kinetochore microtubules extend from a pole to a kinetochore
• polar microtubules extend from a pole to the midplane area, often
overlapping with polar microtubules from the other pole
- The mitosis checkpoint appears to be here; progress past metaphase is
typically prevented until the kinetochores are all attached to microtubules.
Figure 6.3.
5. Characteristics of Anaphase
- Centromeres of each chromosome move apart, Sister chromatids split
into separate chromosomes
- Characteristic “V” shape, Kinetochore fibers move ahead of the
remaining chromosome
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Ass. Lec Ghufran S. Salih Cytology/ Second Stage
2018/ 2019 First semester
University of Warith Al-Anbiyaa College of Engineering Biomedical Engineering
- Kinetochore microtubules shorten at the kinetochore end, Chromosomes
move toward poles
- Cell elongates, Poles move farther apart, Non-kinetochore microtubules
push poles apart
- End of Anaphase, two poles have identical chromosomes. figure 6.3.
Figure 6.3: Mitosis cycle (metaphase, Anaphase, Telophase).
6. Telophase the processes of prophase are reversed
- The mitotic spindle is disintegrated
- The chromosomes decondense
- Nuclear membranes reform around the genetic material to form two
nuclei, each with an identical copy of the genetic information
- Nucleoli reappear, and interphase cellular functions resume. Figure 6.3.
B. Cytokinesis
Cell division ends as the cytoplasm divides into two by the process
of cytokinesis (figure 6.4).
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Ass. Lec Ghufran S. Salih Cytology/ Second Stage
2018/ 2019 First semester
University of Warith Al-Anbiyaa College of Engineering Biomedical Engineering
Cytokinesis in eucaryotic cells is mediated by a contractile ring, which
is composed of actin and myosin filaments and a variety of other
proteins. Actin contracts until the cells pinch apart.
Cytokinesis occurs by a special mechanism in higher-plant cells in
which the cytoplasm is partitioned by the construction of a new cell
wall, the cell plate, inside the cell. The position of the cell plate
is determined by the position of a preprophase band of microtubules
and actin filaments.
Figure 6.4: Cytokinesis
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Ass. Lec Ghufran S. Salih Cytology/ Second Stage
2018/ 2019 First semester
University of Warith Al-Anbiyaa College of Engineering Biomedical Engineering
Lecture Seven… Cell Cycle and Cell Division (b)
Sexual Life Cycles (Meiosis)
Meiosis is the form of eukaryotic cell division that produces haploid sex
cells or gametes (which contain a single copy of each chromosome) from
diploid cells (which contain two copies of each chromosome). The
process takes the form of one DNA replication followed by two
successive nuclear and cellular divisions (Meiosis I and Meiosis II).
- Meiosis involves two sequential cycles of nuclear and cell division
called meiosis I and meiosis II but only a single cycle of DNA
replication.
- Meiosis I is initiated after the parental chromosomes have replicated to
produce identical sister chromatids at the S phase.
- Meiosis involves pairing of homologous chromosomes and
recombination between them.
- Four haploid cells are formed at the end of meiosis II. Meiotic events
can be grouped under the following phases:
Meiosis I Meiosis II
Prophase I Prophase II
Metaphase I Metaphase II
Anaphase I Anaphase II
Telophase I Telophase II
Meiosis I
Meiosis I separates the pairs of homologous chromosomes (Figure 6.5-6).
• Prophase I
Prophase of the first meiotic division is typically longer and more
complex when compared to prophase of mitosis. It has been further
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Ass. Lec Ghufran S. Salih Cytology/ Second Stage
2018/ 2019 First semester
University of Warith Al-Anbiyaa College of Engineering Biomedical Engineering
subdivided into the following five phases based on chromosomal
behaviour, i.e., Leptotene, Zygotene, Pachytene, Diplotene and
Diakinesis.
Leptotene: chromosomes start to condense.
Zygotene: homologous chromosomes become closely associated
(synapsis) to form pairs of chromosomes (bivalents) consisting of four
chromatids (tetrads).
Pachytene: This stage is characterized by the appearance of
recombination nodules (chiasmata), the sites at which crossing over
occurs between non-sister chromatids of the homologous
chromosomes. Crossing over is the exchange of genetic material
between two homologous chromosomes. Crossing over is also an
enzyme-mediated process and the enzyme involved is called
recombinase. Crossing over leads to recombination of genetic
material on the two chromosomes. Recombination between
homologous chromosomes is completed by the end of pachytene,
leaving the chromosomes linked at the sites of crossing over.
Diplotene: homologous chromosomes start to separate but remain
attached by chiasmata.
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Ass. Lec Ghufran S. Salih Cytology/ Second Stage
2018/ 2019 First semester
University of Warith Al-Anbiyaa College of Engineering Biomedical Engineering
Diakinesis: homologous chromosomes continue to separate, and
chiasmata move to the ends of the chromosomes.
• Prometaphase I
Spindle apparatus formed, and chromosomes attached to spindle fibres by
kinetochores.
• Metaphase I
The bivalent chromosomes align on the equatorial plate. The
microtubules from the opposite poles of the spindle attach to the pair of
homologous chromosomes
• Anaphase I
The homologous chromosomes separate, while sister chromatids remain
associated at their centromeres.
• Telophase I
The chromosomes become diffuse and the nuclear membrane reforms.
• Cytokinesis
Cytokinesis follows and this is called as diad of cell. Although in many
cases the chromosomes do undergo some dispersion, they do not reach
the extremely extended state of the interphase nucleus. The stage between
the two meiotic divisions is called interkinesis and is generally short
lived. Interkinesis is followed by prophase II, a much simpler prophase
than prophase I.
Meiosis II
Meiosis II separates each chromosome into two chromatids. The events
of Meiosis II are analogous to those of a mitotic division, although the
number of chromosomes involved has been halved (figure 6.5-6).
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Ass. Lec Ghufran S. Salih Cytology/ Second Stage
2018/ 2019 First semester
University of Warith Al-Anbiyaa College of Engineering Biomedical Engineering
Figure 6.5: Meiosis Cycle in males
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Ass. Lec Ghufran S. Salih Cytology/ Second Stage
2018/ 2019 First semester
University of Warith Al-Anbiyaa College of Engineering Biomedical Engineering
Figure 6.6: Meiosis cycle in female
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Ass. Lec Ghufran S. Salih Cytology/ Second Stage
2018/ 2019 First semester
University of Warith Al-Anbiyaa College of Engineering Biomedical Engineering
Meiosis generates genetic diversity through:
The exchange of genetic material between homologous
chromosomes during Meiosis I.
The random alignment of maternal and paternal chromosomes in
Meiosis I.
The random alignment of the sister chromatids at Meiosis II.
Regulation of the Cell Cycle
The current model of cell cycle regulation involves a highly conserved,
genetically-controlled program that can be influenced by external signals.
Figure 6.7.
1. There are three major checkpoints, found in G1, G2 and mitosis
2. Key regulatory components for checkpoints are cyclins and cyclin-
dependent protein kinases
3. Hormones such as cytokinins in plants and various protein growth
factors in animals can stimulate progression through checkpoints in the
right cells under the right conditions
4. Other factors can serve as suppressors of cell division
5. Cancer cells generally grow without needing stimulation by external
growth factors and fail to respond to normal suppressors of cell division.
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Ass. Lec Ghufran S. Salih Cytology/ Second Stage
2018/ 2019 First semester
University of Warith Al-Anbiyaa College of Engineering Biomedical Engineering
Figure 6.7: Cell Cycle check points