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Transcript
First stage
28/12/2015
Biology
Lec 2
‫ بثينة‬.‫د‬
The nucleus
The Nucleus is highly specialized organelle that serve as the
information processing and administrative center of the cell. This
organelle has two major functions: it stores the cells hereditary material,
or DNA, and it coordinated the cells activities, which include growth,
intermediary metabolism, protein synthesis, and reproduction (cell
division). Its position may change from time to time according to the
metabolic status of the cell. Usually the cells contain single nucleus but
the number of nucleus may vary from cell to cell. On the basis of number
of nuclei present, cells are classified as mononucleate(example;smooth
muscle cell). Binucleate(example; liver cells, cartilage cells) and
polynucleated cells(syncytial cells)(example; osteoclast).The shape of the
nucleus normally related to the shape of the cell, but certain nuclei are
almost irregular in shape. In a tumor, the presence of nuclei with
irregular features (e.g., variable size, atypical chromatin patterns) and the
capacity to invade neighboring tissues are the main morphologic
characteristic used by pathologists to estimate the malignancy.
Ultra structure of the nucleus
The nucleus is composed of four main parts, the nuclear envelope,
nuclear sap or nucleoplasm, the nucleolus and the chromatin fibers.
The nuclear envelope:
The nuclear envelope has a complex structure, consisting of:
(1)- Two nuclear membranes
(2)- Underlying nuclear lamina
(3)- Nuclear pore complexes.
The nuclear envelope is a double-layered membrane that encloses the
content of the nucleus during most of the cell's life cycle. The space
between the layers is called peri-nuclear space and appears to connect
with the rough endoplasmic reticulum, where protein synthesis occurs.
The inner surface has a protein lining called nuclear lamina, which binds
to chromatin and other nuclear components. During mitosis, or cell
(1)
Structure of the nucleus
division, the nuclear envelope disintegrates, but reforms as the two cells
complete their formation.
Lamin gene expression depends on the cell type and stage of
development. All nuclei of higher eukaryotes, including early embryos,
have a lamina that contains lamin B-family subunits, loss of which is
lethal. Lamins A&C typically appear only later in development as cells
begin to differentiate. This variation in lamina composition may affect
chromosome organization, possibly contributing to different patterns of
gene expression.
(2)
Nuclear pores:
The envelope is perforated with tiny holes called nuclear pores. These
pores regulate the passage of molecules between the nucleus and the
cytoplasm
Detailed structural studies indicate that the nuclear pore complex
consists of assembly of eight spokes arranged around a central channel.
The nuclear pores( nuclear pore complex) appear circular in surface
view and have a diameter between 10-100nm.the nuclear pore complex is
generally permeable for molecules of 5-500 Daltons size.
The nucleotides, ions and many other molecules have easy access into the
nucleus. But proteins of more than 50 KD cannot diffuse passively; they
are transported through ATP dependent (active process) pathway.
Nuclear pores
Nucleoplasm:
Nuclear sap is colorless, transparent, granular, semifluid matrix found
inside the nucleus is called nucleoplasm. Within the nucleoplasm, most of
the nuclear material consists of chromatin, the less condensed form of the
cell's DNA that organizes to form chromosomes during mitosis or cell
division. It consists of mainly the nucleoproteins and other organic and
inorganic substances like nucleic acids, proteins, enzymes and minerals.
The nucleolus:
Through the microscope, the nucleolus looks like a large dark spot
within the nucleus, that manufactures ribosomes. The number of nucleoli
in the nucleus depends on the species and the number of chromosomes.
(3)
After a cell division, a nucleolus is formed when chromosomes are
brought into nuclear organizing regions.
Nucleoli are typically composed of three morphologically distinct regions
which can be visualized by electron microscopy(EM):
Fibrillar center(FC):it is highly stained inner most region of nucleolus
composed of fibrils that occupies 1-2% of the total volume. The RNA
genes of nucleolar organizer of chromosomes are located in this region.
Dense fibriller centers(DFC): it surrounds the Fc's, composed of
densely packed fibrils and occupies a large fraction of the nucleolus
(about 17%). The biogenesis of RNA takes place in this region.
Granular region (GR):it is the largest and outer most fraction of the
total nucleolus volume (about 75%). At this region the processing and
maturation of pre-ribosomal particles occurs.
Chromatin and chromosomes:
They are thread-like structures located inside the nucleus of animal
and plant cells. The complexes between eukaryotic DNA& Proteins are
called chromatin, which typically contains about twice as much as much
protein as DNA. The major proteins are the histones, small proteins
containing a high proportion of basic amino acids ( arginine and lysine)
that facilitate binding to the negatively charge DNA molecules, there are
(4)
five major types of histone called H1, H2A, H2B, H3, H4 , which are
very similar among different species of eukaryotes. Histone proteins are
involved in a range of activities, including DNA replication and gene
expression.
Partial digestion of chromatin with micrococcal nuclease, the enzyme
can attack DNA on sites separated by approximately 200 base pairs..
consistent with this notion, electron microscopy revealed that chromatin
fibers have a beaded appearance, with the beads spaced at intervals of
approximately 200 base pairs. Thus, both nuclease digestion and the E.M
studies suggested that chromatin is composed of repeating 200-base pairs
units, which are called (nucleosome).
More extensive digestion of chromatin with micrococcal nuclease was
found to yield particles (nucleosome core particles). Each one contain
146 base pairs of DNA wrapped 1.75 times around a histone core
consisting of two molecules each of the H2A,H2B,H3,H4 (the core
histone).
One molecules of H1 is bound the DNA as it enters and exits each
nucleosome core particles, this form as chromatin subunit known as
(5)
(6)
Structure of nucleosome
(7)
( Chromatosome) consists of 166 base pairs of DNA wrapped around
the histone core held by H1(a linker histone).
Nonhistone proteins are major component of genetic regulatory system,
acting as, activator, inhibitors and enzymes.
The chromatin can then further condensed by coiling into 30nm fibers
(chromosomes). The number and characteristic of chromosomes
encountes in an individual are known as the karyotypes (alterations
associated with ( tumors, leukemia's, and several types of genetic
diseases)
human cell contains 46 chromosomes arranged in 23 pairs, each pair are
identical with each other.
The extent of chromatin condensation varies during the life cycle of the
cell.
In interphase (non living cell) most of the chromatin called
(euchromatin),is genetically active, is relatively decondensed and
distributed through the nucleus. During this period of the cell cycle, gene
are transcribed and the DNA is replicated in preparation for cell division.
A bout 10% of interphase chromatin (called heterochromatin) is a very
highly condensed state that resembles the chromatin of cell undergoing
mitosis.
Genetic defects in nuclear envelope
Genetic defects in nuclear envelope proteins are known to cause at
least 14 disorders, including muscular dystrophies, lipodystrophies, and
neuropathies ( diseases of striated muscle, fatty tissue & the nervous
system). The most dramatic of these is Hutchinson-Gilford progeria.
Affected individuals are essentially normal at birth, but they appear to age
rapidly and die in their early teens of symptoms (including atherosclerosis
& heart failure) that are typically associated with extreme age.
(8)
‫عاند الدنيا وابتسم ان بعد الليل فجر يرتســـم‬
‫التقل حظي قليل انما قل هذا قدري وماقسم‬
‫‪Mohammed J Al-Rawi‬‬
(9)