Cell cycle

1. Cell Biology
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Cell Cycle
 The cell cycle varies in length in different types of cells, but is repeated each time a cell
divides. It is composed of a series of events that prepare the cell to divide into two daughter
cells.
 It is temporarily suspended in nondividing resting cells (e.g., peripheral lymphocytes),
which are in the Go state. Such cells may reenter the cycle and begin to divide again.
 It is permanently interrupted in differentiated cells that do not divide (e.g., cardiac
muscle cells and neurons).
 Two major periods, interphase (interval between cell divisions) and mitosis (M phase, the
period of cell division) compose the cell cycle.
 Interphase is considerably longer than the M phase and is the period during which the cell
doubles in size and DNA content.
1) Interphase is divided into three separate phases (G1, S, and G2), during which specific
cellular functions occur.
1. G1 phase: The GI phase is the gap of time between mitosis (M phase) and DNA
synthesis (S phase). The GI phase is the phase where RNA, protein, and organelle
synthesis occurs. The G, phase lasts about 5 hours in a typical mammalian cell with a
16-hour cell cycle.
2. S phase (synthetic phase) :The S phase is the phase where DNA synthesis occurs. The
S phase lasts about 7 hours in a typical mammalian cell with a 16-hour cell cycle.
3. G2 phase: The G2 phase is the gap of time between DNA synthesis (S phase) and
mitosis (M phase). The G2 phase is the phase where high levels of ATP synthesis
occur. The G2 phase lasts about 3 hours in a typical mammalian cell with a 16-hour cell
cycle.
2) Several control factors have been identified, including a category of proteins known as
cyclins as well as cyclin-dependent kinases (CDKs), which initiate and/or induce
progression through the cell cycle.
 During G1 phase, cyclins D and E bind to their respective CDKs; these complexes
enable the cell to enter and advance through the S phase.
 Cyclin A binds to its CDKs, thus enabling the cell to leave the S phase and enter
the G2 phase, and also to manufacture cyclin B.
 Cyclin B binds to its CDK, inducing the cell to leave the G2 phase and enter the M
phase.

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 Mitosis: The M phase is the phase where cell division occurs. The M phase is divided
into six stages called prophase, prometaphase, metaphase, anaphase, telophase,
and cytokinesis. The M phase lasts about 1 hour in a typical mammalian cell with a 16-
hour cell cycle.
o Prophase. The chromatin condenses to form well-defined chromosomes. Each
chromosome has been duplicated during the S phase and has a specific DNA
sequence called the centromere that is required for proper segregation. The
centrosome complex, which is the microtubule organizing center (MTOC), splits into
two, and each half begins to move to opposite poles of the cell. The mitotic spindle
(microtubules) forms between the centrosomes.
o Prometaphase. The nuclear envelope is disrupted, which allows the microtubules access
to the chromosomes. The nucleolus disappears. The kinetochores (protein complexes)
assemble at each centromere on the chromosomes. Certain microtubules of the mitotic
spindle bind to the kinetochores and are called kinetochore microtubules. Other
microtubules of the mitotic spindle are now called polar microtubules and astral
microtubules.
o Metaphase. The chromosomes align at the metaphase plate. The cells can be
arrested in this stage by microtubule inhibitors (e.g., colchicine).
o Anaphase. The centromeres split, kinetochores separate, and chromosomes move to
opposite poles. The kinetochore microtubules shorten. The polar microtubules lengthen.
o Telophase. The chromosomes begin to decondense to form chromatin. The nuclear
envelope re-forms. The nucleolus reappears. The kinetochore microtubules disappear.
The polar microtubules continue to lengthen.
o Cytokinesis. The cytoplasm divides by a process called cleavage. A cleavage furrow
forms around the middle of the cell. A contractile ring consisting of actin and myosin
filaments is found at the cleavage furrow.
It appears that at the end of cytokinesis the "mother centriole" of the duplicated pair
moves from the newly forming nuclear pole to the intercellular bridge. This event is necessary
to initiate disassembly of the midbody microtubules and the complete separation of the
daughter cells. If this event fails, DNA replication is arrested at one of the G1 checkpoints
during the next interphase.

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Apoptosis (Programmed Cell Death)
Apoptosis is the method whereby cells are removed from tissues in an orderly fashion, as a
part of normal maintenance or during development.
 There are several morphological features of cells that undergo programmed cell death.
 They include chromatin condensation, breaking up of the nucleus, and blebbing of
the plasma membrane.
 Shrinkage of the cell occurs, and it is fragmented into membrane-enclosed
fragments called apoptotic bodies.
 Apoptotic cells do not pose a threat to surrounding cells because changes in their
plasma membranes make them subject to rapid phagocytosis by macrophages and by
neighboring cells.
 The signals that induce apoptosis may occur through several mechanisms.
 Genes that code for enzymes, called caspases, play an important role in the
process.
 Certain cytokines, such as tumor necrosis factor (TNF), may also activate
caspases that degrade regulatory and structural proteins in the nucleus and
cytoplasm, leading to the morphological changes characteristic of apoptosis.
 Defects in the process of programmed cell death contribute to many major diseases.
 Too much apoptosis causes extensive nerve cell loss in Alzheimer disease and
stroke.
 Not enough apoptosis has been linked to cancer and other autoimmune diseases.
Meiosis
 Meiosis is a special form of cell division in germ cells (oogonia and spermatozoa) in
which the chromosome number is reduced from diploid (2n) to haploid (n).
 It occurs in developing germ cells in preparation for sexual reproduction.
Subsequent fertilization results in diploid zygotes.
 The DNA content of the original diploid cell is doubled (4n) in the S phase
preparatory to meiosis.
This phase is followed by two successive cell divisions that give rise to four haploid
cells. In addition, recombination of maternal and paternal genes occurs by crossing over and
random assortment, yielding the unique haploid genome of the gamete.
 The stages of meiosis are meiosis I (reductional division) and meiosis II (equatorial
division).
A. Reductional division (meiosis I) occurs after interphase when the 46 chromosomes are
duplicated, giving the cell a 4CDNA content (considered to be the total DNA content of
the cell).
1) Prophase I is divided into five stages (leptotene, zygotene, pachytene, diplotene, and
diakinesis), which accomplish the following events.
 Chromatin condenses into the visible chromosomes, each containing two
chromatids joined at the centromere.
 Homologous maternal and paternal chromosomes pair via the synaptonemal
complex, forming a tetrad. Crossing over (random exchanging of genes between
segments of homologous chromosomes) occurs at the chiasmata, thus increasing
genetic diversity.
 The nucleolus and nuclear envelope disappear.

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2) Metaphase I
 Homologous pairs of chromosomes align on the equatorial plate of the spindle in
a random arrangement, facilitating genetic mixing.
 Spindle fibers from either pole attach to the kinetochore of any one of the
chromosome pairs, thus ensuring that genetic mixing occurs.
3) Anaphase I
This phase is similar to anaphase in mitosis except that each chromosome consists of two
chromatids that remain held together. Chromosomes migrate to the poles.
4) Telophase I is similar to telophase in mitosis, in that the nuclear envelope is
reestablished and two daughter cells are formed via cytokinesis.
Each daughter cell now contains 23 chromosomes (n) number, but has a 2CDNA content (the
diploid amount). Each chromosome is composed of two similar sister chromatids (not
genetically identical).
B. Equatorial division (meiosis II) begins soon after the completion of meiosis I,
following a brief interphase without DNA replication.
 The sister chromatids are portioned out among the two daughter cells formed in
meiosis I. The two daughter cells then divide, resulting in the distribution of
chromosomes into four daughter cells, each containing its own unique
recombined genetic material (1CDNA;n).
 The stages of meiosis II are similar to those of mitosis; thus the stages are
named similarly (prophase II, metaphase II, anaphase II, and telophase II).
 Meiosis II occurs more rapidly than mitosis.
Clinical Considerations
Aneuploidy is defined as an abnormal number of chromosomes and can be detected by
karyotyping. Examples include trisomy (the presence of a third chromosome of one type)
and monosomy (the absence of one member of a chromosome pair).
 Down syndrome (trisomy 21) is characterized by mental retardation, short stature,
stubby appendages, congenital heart malformations, and other defects.
 Klinefelter syndrome (XXY) is aneuploidy of the sex chromosomes, characterized by
infertility, variable degrees of masculinization, and small testes.
 Turner syndrome (XO) is monosomy of the sex chromosomes, characterized by short
stature, sterility, and various other abnormalities.
Transformed cells
 Transformed cells have lost their ability to respond to regulatory signals controlling the
cell cycle. They may undergo cell division indefinitely, thus becoming cancerous.
 Vinca alkaloids may arrest these cells in mitosis; drugs that block purine and
pyrimidine synthesis may arrest cells in the S phase of the cell cycle.
Oncogenes represent mutations of certain regulatory genes, called proto-oncogenes,
which normally stimulate or inhibit cell proliferation and development.
 Genetic accidents or viruses may lead to the formation of oncogenes.
 Oncogenes dominate the normal alleles (proto-oncogenes), causing a deregulation of
cell division, which leads to a cancerous state.
 Bladder cancer and acute myelogenous leukemia are caused by oncogenes.