Chapter 3
The Nucleus
Nucleus
• command center of the cell containing the code
for all of a cell’s enzymes and other proteins
• contains the molecular machinery to replicate
the DNA and to synthesize and process all types
of RNA
Components of the Nucleus
1. Nuclear Envelope
• forms a selectively permeable barrier
between the nuclear and cytoplasmic
compartments.
• a double set of membranes with a narrow
perinuclear space; the outer membrane
binds ribosomes and is continuous with the
RER.
• nuclear envelope is supported internally by a
meshwork, the nuclear lamina, composed of
intermediate filament subunits called
lamins.
• the nuclear envelope is penetrated by
nuclear pore complexes, large assemblies of
nucleoporins (core proteins of a nuclear pore
complex) with eightfold symmetry through
which proteins and protein–RNA complexes
movement is regulated.
• Macromolecules shipped out of the nucleus
include ribosomal subunits and other RNAs
associated with proteins, while inbound
traffic consists of chromatin proteins,
ribosomal proteins, transcription factors,
and enzymes. They bind with transport
proteins called importins that in turn
interact with proteins of the pore complexes
for transfer across the nuclear envelope.
2. Chromatin
• consists of DNA and all of the associated
proteins involved in the organization and
function of DNA
• Chromatids – two identical chromatin
units held together by complexes of
cohesion proteins after DNA replication
before cell division
• Histones – sets of small basic proteins
where the DNA molecule molecule
initially wraps
• Nucleosomes - structural unit of DNA
and histones
• In the EM the series of nucleosomes on
DNA resembles “beads on a string,”
2 categories of chromatin
1. Euchromatin - visible as finely dispersed
granular material in the electron microscope
and as lightly stained basophilic areas in the
light microscope
2. Heterochromatin - r. heteros, other +
chroma, color) appears as coarse, electron-
dense material in the electron microscope
and as intensely basophilic clumps in the
light microscope.
- always more compact than
euchromatin, shows little or no
transcriptional activity, and includes at
least two types of genomic material
called constitutive and facultative
heterochromatin
- Constitutive heterochromatin is
generally similar in all cell types and
contains mainly repetitive, gene-poor
DNA sequences, including the large
chromosomal regions called
centromeres and telomer
- Facultative heterochromatin contains
other regions of DNA with genes where
transcription is variably inactivated in
different cells by epigenetic mechanisms
- Euchromatin predominates in active
cells such as large neurons, while
heterochromatin is more abundant in
cells with little synthetic activity such as
circulating lymphocytes
- Barr body – small dense sex chromatin
which is one of the two large X
chromosomes present in human females
but not male
The Cell Cycle
Nucleolus
• the nucleolus is a very basophilic or electron-
dense area of chromatin localized actively
engaged in protein synthesis.
• Densely concentrated ribosomal RNA (rRNA)
that is transcribed, process and assembles
into ribosomal units are localized
• By TEM, an active nucleolus is seen to have
fibrous and granular parts where rRNA forms
and ribosomal subunits are assembled,
respectively
•
• is the sequence of events that controls cell
growth and division forming new cells
• G1 phase, the longest part of the cycle, and
period of active RNA and protein synthesis. Cell
volume reduced by half after mitosis
• S phase is the period of DNA replication, histone
synthesis, and beginning of centrosome
duplication
• In a short G2 phase, proteins required for mitosis
accumulate
 • Cycling is activated in postmitotic G0 cells by
protein signals from the extracellular
environment called mitogens or growth factors
that bind to cell surface receptors and trigger a
cascade of kinase signaling in the cells.
• Cyclins – a cytoplasmic proteins that regulates
the entry or progression through other phases of
the cycle by activating cyclin-dependent kinases
(CDKs) which phosphorylates specific proteins
triggering next phase of the cycle
• Progress through the cell cycle stages is
monitored at checkpoints, including the G1
restriction point; only when each phase’s
activities are completed are the cyclins changed
to trigger those of the next phase
• Rb protein and p53
• Metaphase - chromosomes condense further
and large protein complexes called kinetochores
attach to the mitotic spindle
• Anaphase - sister chromatids (now called
chromosomes themselves) separate and move
toward opposite spindle poles
• Telophase - two sets of chromosomes are at the
spindle poles and begin reverting to their
uncondensed state, Microtubules of the spindle
depolymerize and the nuclear envelope begins
to reassemble around each set of daughter
chromosomes
• cytokinesis at the end of telophase, constriction
of this ring produces a cleavage furrow and
progresses until the cytoplasm and its organelles
are divided into two daughter cells, each with
one nucleus.

Mitosis

• Prophase – nucleolus disappears, replicated

chromatin condenses into threadlike
chromosomes, each consisting of duplicate sister
chromatids joined at the centromere. The 2
centrosomes separate and migrate to opposite
poles and organize the microtubules of the
mitotic spindle
• Late prophase - lamins and inner nuclear
membrane are phosphorylated, causing the
nuclear lamina and nuclear pore complexes to
disassemble and disperse
 • The second meiotic division occurs with no
Stem Cells & Tissue Renewal
• Stem cells occur in all tissues with rapid cell
turnover; they divide slowly in an asymmetric
manner, with one daughter cell remaining a stem
cell and one becoming committed toward
differentiation.
• Cells committed to differentiate (transit
amplifying or progenitor cells) typically divide
more rapidly than stem cells before slowing or
stopping division to differentiate
Apoptosis
Meiosis
• process by which two successive cell divisions
produce cells called gametes containing half the
number of chromosomes found in somatic cells.
• Prophase of the first meiotic division is a unique,
extended period in which homologous
chromosomes pair and undergo genetic
recombination during the process called
synapsis where crossovers occur
• Synaptic pairs separate toward two daughter
cells at the first meiotic division
intervening S phase and separates the sister
chromatids into two final cells that are haploid.
• is the process by which redundant or
defective cells are rapidly eliminated in a
manner that does not provoke a local
infammatory reaction in the tissue
• It results in small membrane-enclosed
apoptotic bodies, which quickly undergo
phagocytosis by neighboring cells or cells
specialized for debris removal
• Necrosis occur when cells die as a result of
injury which then triggers a local
inflammatory reaction and immigration of
leukocytes.
• Apoptosis involves a cascade of events
controlled by the Bcl-2 family of proteins
regulating the release of death-promoting
factors from mitochondria.
• Cytochrome c from mitochondria activates
cytoplasmic proteases called caspases,
which degrade proteins of the cytosol,
cytoskeleton, and cell membrane
• Endonucleases are activated, which degrade
all nuclear DNA
• Cell and nuclear volumes shrink rapidly, and
the cell membrane changes produce
extensive blebbing of the cell surface.
• Late in apoptosis, the cell breaks into many
small apoptotic bodies that undergo
phagocytosis by neighboring cells
• Apoptosis occurs rapidly, with little or no
release of proteins that would trigger
in$ammation, unlike the death of injured
cells by necrosis that typically induces local
in$ammation