UNIT 3: NUCLEUS

THE NUCLEUS The outer membrane bound to it and is continuous with the ER.
• Occurs in most cells except bacteria The two membranes fuse at many places to form nuclear pores.
• Separated from the rest of the cell by the nuclear Heterochromatin clumps (HC) are associated with the
membrane which is continuous to the endoplasmic meshwork of the nuclear lamina just envelope, whereas the
reticulum euchromatin (EC) appears dispersed in the interior of the
nucleus. The nucleolus contains distinct regions called the pars
Overview of the Nucleus granulosa (G) and the pars fibrosa (F).
• The nucleus contains a blueprint for all cell structures and
activities encoded in the DNA of the chromosomes. • Nuclear lamina – supports the nuclear envelope
• It also contains the molecular machinery to replicate its • Heterochromatin – electron dense areas; appear dark
DNA and to synthesize an RNA. • Nuclear pores – serves as a pathway hence it has no
• Nucleus carries the gene (hereditary information) chromatin; portion where the inner and outer membrane
• It controls and regulates activities of the cell like growth meets and form spaces
and metabolism • Perinuclear space – separates the inner and outer
• It provides information needed by the cell to perform its membrane
functions • Pars granulosa is denser and is granular while Pars
fibrosa is less dense and is fibrous
Components of the Nucleus
• Nuclear envelope Clinical Significance
• Chromatin • Simple microscopic evaluation of the nucleus provides a
• Nucleolus great deal of information about cell well-being. Evaluation
• Eccentric – nucleus at the of nuclear size, shape, and structure plays an important role
peripheral part in tumor diagnosis. Nuclear alterations in dying cells:
• Centric – nucleus at the o Karyolysis, or the disappearance of nuclei due to
central part complete dissolution of DNA by increased activity
• If Cell: Cytoplasm then of DNAase ( DNAse = nuclei disappearance)
Nucleus: Nucleolema → o Pyknosis, or condensation of chromatin leading
contains chromatin dispersed in the nucleus to shrinkage of the nuclei (they appears as dense
basophilic masses)
Functions of the Nucleus o Karyorrhexis, or fragmentations of nuclei
1. Cellular regulation: houses genetic material, which directs o These three are important in disease diagnosis,
all cellular activities and regulates cellular structure especially in tumor and cancer diagnosis
2. Production: Produces ribosomal subunits in nucleolus and
exports them into cytoplasm for assembly into ribosomes Nuclear Envelope
• Selectively permeable membrane that is seven times
(a): TEM of a typical cell nucleus clearly shows the electron- thicker than plasma membrane and perforated by nuclear
dense heterochromatin (HC) and the more diffuse pores
euchromatin (EC). The arrows indicate the nucleolus- • EM: has two eccentric membranes separated by
associated heterochromatin perinuclear space
around. Arrowheads indicate o The outer nuclear membrane is continuous with
areas where the perinuclear space rER membrane. It has attached polyribosomes
between the two membranes of the o The inner nuclear membrane is supported by a
nuclear envelope is clearly seen. rigid network of intermediate protein filaments
Just inside the nuclear envelope is attached to its inner surface called the nuclear
a thin electron-dense region (fibrous) lamina
containing and more ▪ contains specific lamin receptors and
heterochromatin. X26, 000. several lamina- associated proteins that
bind to chromosomes and secure the
Note: Heterochromatin is denser than euchromatin. The dark attachment of the nuclear lamina
areas are the HC while the (purpose)
granules around the dark areas • Nuclear lamina. The nuclear
are the EC lamina is formed from a class of
intermediate filaments proteins,
(b): Schematic the lamins, which assemble as a
representation of a cell lattice adjacent to the inner
nucleus shows that the nuclear membrane. When the
nuclear envelope is made of nuclear envelope disperses of
two membranes separated cell division, at least some lamin
by the perinuclear space. proteins remain attached to the

Pader, Juliene Andrei B.

 Nucleus
membrane fragments and reassembly of the nuclear lamina
immediately after cell division facilitates re-formation of the
nuclear envelope new nuclei. The nuclear lamina also
contains binding sites for chromatin, helping to organize this
material in the nucleus. Chromatin is not present at the
openings through the nuclear envelope called pore
complexes.
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
muscular dystrophy (EDMD) have been associated with
mutations in either lamins or lamin receptors.
• EDMD – muscle weakness; contractures of major tendons;
genetic disease; due to impairment of nuclear lamina called
laminopathy (rare genetic disorders caused by mutations in
genes encoding proteins of the nuclear lamina).
• 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
• In nondividing cells, consists of the DNA and its attendant
protein in a largely uncoiled state
• Negatively charged
• 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
• The smallest units of chromatin structure macromolecular
complexes of DNA and histones called nucleosomes
• Chromatin is made of chains of nucleosome; if it loosens
there will be unwrapping of DNA
• 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.
• 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
Pader, Juliene Andrei B.
• 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.
• 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 ( telomere =  lifespan;  means longer)
• 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 (telomeres lengthen). Recently, expression of this
enzyme has been shown to extend the lifespan of cells.
• 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
• 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
Two types:
• Heterochromatin
o EM: appear as coarse electron-dense material
o LM: basophilic clumps → absorbs positively
charged stains
o “Barr bodies”, dense mass of heterochromatin
found in females
o Predominant in metabolically inactive cells; cells
not active in cell cycle (e.g. lymphocytes, plasma
cells, sperm)
o Appear as dark areas since they are compact or
dense.
o Dense: not ready or destined for reading and
transcription
 Nucleus
• Euchromatin
o EM: finely dispersed granular material
o LM: lightly stained basophilic areas
o Active chromatin: metabolically active (e.g.
neurons, liver cells)
o Stretched out hence genetic information in DNA
can be read and transcribed
o Ready for reading and transcription
Nucleolus
• Nucleolus is a spherical, highly basophilic sub domain of
nuclei in cells, actively making proteins
• It is a nonmembranous
region of the nucleus that
surrounds
transcriptionally active
rRNA genes.
• It is the primary site of
ribosomal production and
assembly.
• The nucleolus is the site of ribosomal RNA (rRNA)
synthesis and initial ribosomal assembly; final assembly:
cytoplasm outside the nucleus
• Ribosomal proteins are actually synthesized in the
cytoplasm and being transferred in the nucleus for sub-
assembly or nucleolus (initial assembly).
• The nucleolus varies in size but is particularly well
developed in cells active in protein synthesis
• Some cells contain more than one nucleolus
The three morphologically distinct regions of nucleolus:
• Fibrillar centers contain DNA loops of five different
chromosomes (13, 14, 15, 21, and 22) that contain rRNA
genes, RNA polymerase I, and transcription factors
• Fibrillar material (pars fibrosa) contain ribosomal genes
that are actively undergoing transcription and large
amounts of rRNA
• Granular material (pars granulosa) represents the site of
initial ribosomal assembly and contains densely packed
preribosomal particles
• 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.
• Fibrillar (F) material – contains genes undergoing
transcription and large amount of RNA
• Granular (G) material – site of initial ribosomal assembly;
densely packed free ribosomal particles
Pader, Juliene Andrei B.
Cell Death
• In humans, as in all other multicellular organisms, the rates
of cell proliferation and cell death determine the net cell
production.
o disorders of cell accumulation (e.g., hyperplasia,
cancer, autoimmune diseases)
o disorders of cell loss (atrophy, degenerative
diseases, AIDS, ischemic injury). Persons with
HIV do not immediately acquire AIDS. AIDS will
only develop if the CD4 cells decreased. When the
level of the CD4 cells decreases that is the time
where the patients acquire increase susceptibility
of infection.
• Note: There should be balance or homeostasis in cell
division and cell death. Why? Because if there is an
increase cell loss of course it will result to diseases like
AIDS, Alzheimer’s, and Parkinson’s that lead to damage of
nervous system cells.
Two Major Mechanisms of Cell Death
• Necrosis, or accidental cell death, is a pathologic process.
o It occurs when cells are exposed to an unfavorable
physical or chemical environment that causes
acute cellular injury and damage to the plasma
membrane.
o Damage to the plasma membrane may also be
initiated by viruses, or proteins called perforins.
o Characteristic feature: Rapid cell swelling and
lysis
• Apoptosis [Gr., falling off, as petals from flowers] was
referred to in the past as programmed cell death
o It is characterized by controlled autodigestion or
self digestion
o The cell “dies with dignity” without spilling its
contents and damaging its neighbors. The cell
releases the lytic enzymes on itself without
releasing it to the neighboring cells which means
siya lang ang affected.
o no damage in cell membrane
o bleb formation → apoptotic bodies
Morphologic and Biochemical Features of Apoptosis
• DNA fragmentation
o an irreversible event that commits the cell to die.
o – a result of Ca2-dependent and Mg2-dependent
activation of nuclear endonucleases
• Decrease in cell volume is achieved by shrinking of the
cytoplasm (damage of cytoskeletal elements)
o cytoskeletal elements become reorganized
o ribosomes become clumped within the cytoplasm
o rER forms a series of concentric whorls, and most
of the endocytotic vesicles fuse with the plasma
membrane
 Nucleus

• Loss of mitochondrial function

o 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

• Necrosis
- E.g. Infection
- Pathologic
- bursting; lumalabas yung components ng cell
- injury to the cell membrane
- swelling or inflammation
- membrane breakdown
- disintegration and inflammation
• Apoptosis
- E.g. shedding of skin cells
- natural occurrence
- Programmed cell death
- DNA fragmentation
shrinkage of cytoplasm due to the reorganization of the
plasma membrane
- membrane blebbing
- formation of apoptotic bodies

Pader, Juliene Andrei B.