THE CELL NUCLEUS 18/02/2020

OVERVIEW OF THE NUCLEUS

• The nucleus contains a blueprint for all cell

THE structures and activities encoded in the DNA of

the chromosomes.
• It also contains the molecular machinery to

NUCLEUS replicate its DNA and to synthesize an RNA.

(a): TEM of a typical cell nucleus clearly shows the electron-dense heterochromatin (HC) and the more
diffuse euchromatin (EC). The arrows indicate the nucleolus-associated heterochromatin around.
Arrowheads indicate areas where the perinuclear space between the two membranes of the nuclear envelope
Components of the nucleus: is clearly seen. Just inside the nuclear envelope is a thin electron-dense region containing and more
heterochromatin. X26,000. (b): Schematic representation of a cell nucleus shows that the nuclear
Nuclear envelope envelope is made of two membranes separated by the perinuclear space. The outer membrane- bound
to it and is continuous with the ER. The two membranes fuse at many places to form nuclear pores.
chromatin Heterochromatin clumps (HC) are associated with the meshwork of the nuclear lamina just envelope, whereas
the euchromatin (EC) appears dispersed in the interior of the nucleus. The nucleolus contains distinct regions
nucleolus called the pars granulosa (G) and the pars fibrosa (F).

CLINICAL SIGNIFICANCE
• Simple microscopic evaluation of the nucleus provides
a great deal of information about cell well-being.
Evaluation of nuclear size, shape, and structure plays
an important role in tumor diagnosis. Nuclear
alterations in dying cells: NUCLEAR
– karyolysis, or the disappearance of nuclei
due to complete dissolution of DNA by
increased activity of DNAase
ENVELOPE
– pyknosis, or condensation of chromatin
leading to shrinkage of the nuclei (they
appears as dense basophilic masses)
– karyorrhexis, or fragmentations of nuclei

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NUCLEAR ENVELOPE Nuclear lamina. The nuclear

lamina is formed from a class of
intermediate filaments proteins,
• Selectively permeable membrane that is seven times the lamins, which assemble as
thicker than plasma membrane and perforated by a lattice adjacent to the inner
nuclear membrane. When the
nuclear pores nuclear envelope disperses of
• EM: has two eccentric membranes separated by cell division, at least some
lamin proteins remain attached
perinuclear space to the membrane fragments
– The outer nuclear membrane is continuous with rER and reassembly of the nuclear
lamina immediately after cell
membrane. It has attached polyribosomes division facilitates re-formation
– The inner nuclear membrane is supported by a rigid of the nuclear en new nuclei.
The nuclear lamina also
network of intermediate protein filaments attached to contains binding sites for
its inner surface called the nuclear (fibrous) lamina chromatin, helping to organize
this material in the nucleus.
• contains specific lamin receptors and several Chromatin is not present at the
lamina-associated proteins that bind to openings through the nuclear
chromosomes and secure the attachment of the envelope called pore
complexes.
nuclear lamina

CLINICAL SIGNIFICANCE
• Impairment in nuclear lamina architecture or function is
associated with certain genetic diseases (laminopathies)
and apoptosis. Mutations in lamin A/C cause tissue-
specific diseases that affect striated muscle, adipose
tissue, peripheral nerve or skeletal development, and
premature aging.
• Recently, two hereditary forms of Emery-Dreifuss
CHROMATIN
muscular dystrophy (EDMD) have been associated
with mutations in either lamins or lamin receptors.
• In general, EDMD is characterized by an early-onset
contractures of major tendons, very slow progressive
muscle weakness, muscle wasting in the upper and
lower limbs, and cardiomyopathy (weakening of the
heart muscle).

CHROMATIN CHROMATIN
• In nondividing cells, consists of the DNA and Euchromatin indicates active chromatin—that
its attendant protein in a largely uncoiled is, chromatin that is stretched out so that the
state genetic information in the DNA can be read and
– Two type:
transcribed.
• Heterochromatin- EM: appear as coarse
electron-dense material It is prominent in metabolically active cells such
– LM: basophilic clumps as neurons and liver cells.
– ―Barr bodies‖, dense mass of heterochromatin
found in females
• Euchromatin- EM: finely dispersed granular Heterochromatin predominates in metabolically
material inactive cells such as small circulating
– LM: lightly stained basophilic areas lymphocytes and sperm or in cells that produce
one major product such as plasma cells.

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THE CELL NUCLEUS
CHROMATIN
• Cells with lightly stained nuclei are more
active in protein synthesis
• In light stained nuclei, with much euchromatin
and few heterochromatic clumps, more DNA
surface is available for transcription
• In dark-stained nuclei rich in highly
condensed heterochromatin, tightly coiled
DNA is less accessible for transcription
• In dividing cells,
chromatin is condensed
and organized into
discrete bodies called
chromosomes
• Each chromosome is
formed by two
chromatids that are
joined together at a point
called the centromere
Packaging of chromatin into the
chromosomal structure. Sequential
steps in the packaging of nuclear
chromatin are shown in this diagram,
beginning with the DNA double helix
and ending with the highly condensed
form found in chromosomes
CHROMATIN
• Human somatic cells contain 46 chromosomes
organized as 23 homologous pairs
• Twenty-two pairs have identical chromosomes
(i.e., each chromosome of the pair contains the
same portion of the genome) and are called
autosomes
• The twenty-third pair of chromosomes are the
sex chromosomes
• The chromosomal number found in most of the
somatic cells of the body and is called the
diploid (2n) number
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• The smallest units
of chromatin
structure are
macromolecular
complexes of
DNA and histones
called
nucleosomes
Nucleosome is a structure that produces the initial organization of free double-
stranded DNA into chromatin. Each nucleosome has an octomeric core
complex made up of four types of histones, two H2B, H3, and H4. Around this
core is wound DNA approximately 150 base pairs in length. One H1 histone is
located outside the DNA on the surface of each nucleosome. DNA associated
with nucleosome resembles a long string of beads. Nucleosomes are very
dynamic structures, with H1 loosening and DNA unwrapping at least once every
second to allow other proteins, including transcription factors to the DNA.
CHROMATIN
• Telomere area located at each end of the chromosome
• shorten with each cell division; studies indicate that
telomere length is an important indicator of the lifespan
of the cell
• cells must activate a mechanism that maintains telomere
length to become immortalized
• For example, in cells that have been transformed into
malignant cells, an enzyme called telomerase is present
that adds repeated nucleotide sequences to the telomere
ends. Recently, expression of this enzyme has been
shown to extend the lifespan of cells.
CHROMATIN
• Eggs and sperm have only 23 chromosomes,
the haploid (1n) number, as well as the
haploid (1d) amount of DNA.
• The somatic chromosome number are
reestablished at fertilization by the fusion of the
sperm nucleus with the egg nucleus
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NUCLEOLUS
• Nucleolus is a spherical,
highly basophilic sub
domain of nuclei in cells,
actively making proteins
NUCLEOLUS • It is a nonmembranous
region of the nucleus
that surrounds
transcriptionally active
rRNA genes.
• It is the primary site of
ribosomal production and
assembly.

NUCLEOLUS NUCLEOLUS
• The nucleolus is the site of ribosomal • The three morphologically distinct
regions of nucleolus:
RNA (rRNA) synthesis and initial – Fibrillar centers contain DNA loops of five
ribosomal assembly different chromosomes (13, 14, 15, 21, and 22)
that contain rRNA genes, RNA polymerase I,
• The nucleolus varies in size but is and transcription factors
particularly well developed in cells active – Fibrillar material (pars fibrosa) contain
ribosomal genes that are actively undergoing
in protein synthesis transcription and large amounts of rRNA
• Some cells contain more than one – Granular material (pars granulosa) represents
the site of initial ribosomal assembly and
nucleolus contains densely packed preribosomal particles

CELL DEATH
Electron micrograph of the nucleolus. This nucleolus from a nerve cell shows
fibrillar centers (FC) surrounded by the fibrillar (F) and granular (G) materials.
Such a network of both materials is referred to as the nucleolonema. The rRNA,
DNA-containing genes for the rRNA, and specific proteins are localized in the
interstices of the nucleolonema. 15,000.

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THE CELL NUCLEUS
CELL DEATH
• In humans, as in all other multicellular
organisms, the rates of cell proliferation
and cell death determine the net cell
production.
– disorders of cell accumulation (e.g.,
hyperplasia, cancer, autoimmune diseases)
– disorders of cell loss (atrophy, degenerative
diseases, AIDS, ischemic injury)
TWO MAJOR MECHANISMS OF
CELL DEATH
• NECROSIS, or accidental cell death, is a
pathologic process.
• It occurs when cells are exposed to an
unfavorable physical or chemical environment
that causes acute cellular injury and damage to
the plasma membrane.
• It begins with impairment of the cell’s ability to
maintain homeostasis
• Damage to the plasma membrane may also be
initiated by viruses, or proteins called perforins.
• Characteristic feature: Rapid cell swelling and
lysis
MORPHOLOGIC AND BIOCHEMICAL
FEATURES OF APOPTOSIS
• DNA fragmentation
– an irreversible event that commits the cell to
die.
– a result of Ca2- dependent and Mg2-
dependent activation of nuclear
endonucleases
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TWO MAJOR MECHANISMS OF
CELL DEATH
• Apoptosis [Gr., falling off, as petals from
flowers] was referred to in the past as
programmed cell death
• It is characterized by controlled
autodigestion
• The cell ―dies with dignity‖ without spilling
its contents and damaging its neighbors
MORPHOLOGIC AND BIOCHEMICAL
FEATURES OF APOPTOSIS
• Decrease in cell volume is achieved by
shrinking of the cytoplasm
– cytoskeletal elements become reorganized
– ribosomes become clumped within the
cytoplasm
– rER forms a series of concentric whorls, and
most of the endocytotic vesicles fuse with the
plasma membrane
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THE CELL NUCLEUS 18/02/2020

MORPHOLOGIC AND BIOCHEMICAL

FEATURES OF APOPTOSIS
• Loss of mitochondrial function
– caused by changes in the permeability of the
mitochondrial membrane channels
• Membrane blebbing results from cell
membrane alterations
• Formation of apoptotic bodies, the final
step of apoptosis, results in cell breakage