1. Cell Biology Lec.No.4 Dr: Buthaina Al-Sabawi Date: 21-11-2010
The Nucleus
The largest and most easily seen organelle within a eukaryotic cell is the nucleus. They are typically located in the central region of the cell, diameter (5-10 µm)
Nuclei are roughly spherical or elongated structure, (uniform with rare exception)

3. In a tumor, the presence of nuclei with irregular features (e. g
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 degree of malignancy. Nucleus serves both as the storage of genetic information and as the cell control center DNA replication Transcription RNA processing all takes place within the nucleus, with only the final stage of gene expression (translation), localized to the cytoplasm.

4. The nucleus comprises - Nuclear envelope:
The nuclear envelope, chromatin, nucleolus, and nuclear matrix.
- Nuclear envelope:
Separates the contents of the nucleus from the cytoplasm.
Acting as barrier to prevent the free passage of molecules.

5. The nuclear envelope has a complex structure, consisting of: (1)- Two nuclear membranes (2)- Underlying nuclear lamina (3)- Nuclear pore complexes. The nucleus is surrounded by a system of two concentric membrane, called the inner and outer nuclear membrane. The outer membrane is continuos with RER, ribosomes on the outer membrane release proteins into the perinuclear (cisternia), the inner membrane is associated with lamina (intermediate filament proteins, lamins)

6. 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.

7. Depending on their size, molecules can travel through the nuclear pore complex by one of two different mechanisms. Small molecules pass rapidly across the nuclear envelope in either direction: cytoplasm to nucleus or nucleus to cytoplasm.
Macromolecules pass through the nuclear complex by an active process.

9. Nuclear pores
Scattered over the surface of the nuclear envelope are shallow depression called nuclear pores.
The nuclear pore complexes are the only channels through which small polar molecules, ions, and macromolecules (proteins and RNAs) are able to travel between the nucleus and the cytoplasm.
Circular Gaps, not open.
Detailed structural studies indicate that the nuclear pore complex consists of assembly of eight spokes arranged around a central channel.

12. Chromatin & chromosome
The complexes between eukaryotic DNA& Proteins are called chromatin,which typically contains about twice as much as much protein as DNA

13. 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 five major types of histone called H1, H2A, H2B, H3, H4 , which are very similar among different species of eukaryotes.

15. 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).

16. 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
( Chromatosome)consists of 166 base pairs of DNA wrapped around the histone core held by H1(a linker histone).

19. The chromatin can then further condensed by coiling into 30nm fibers(chromosomes)
Nonhistone proteins are major component of genetic regulatory system, acting as
1- Activators
2-Inhibitors
3- Enzymes
Double helix is folded or coiled like a spring

21. 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.

22. 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.

23. Nucleolus
Nucleolus, is the most prominent structure within the nucleus, which is the site of rRNA transcription and processing, and of ribosome assembly.
Basophilic ( H & E)
Nucleolus is a ribosome production factory .
Morphologically, nucleoli consist of three distinguishable regions, the fibrillar center, contain concentrations of rRNA genes, together with significant amount of RNA polymerase I and its associated transcription factors.

24. , dense fibrillar components and granular component, is the site for many steps in ribosome subunit assembly and is made up of densely packed clusters of preribosomal particles 15 to 20 nm in diameter. These different regions are thought to represent the sites of progressive stages of rRNA transcription, processing, and ribosome assembly.
Human have approximately 300 t0 400 copies of the ribosomal DNA (rDNA) repeat unit located in clusters on chromosomes 13,14,15,21 and 22 .

25. The size of the nucleolus depends on the metabolic activity of cell
The size of the nucleolus depends on the metabolic activity of cell. Large nucleolus( embryonic cells, cells that are actively synthesizing proteins, malignant tumors). N. disappear, reappears during cell division.

26. Nuclear Matrix
N.M. is defined as the structural skeleton of the nucleus.
Fills the space between the chromatin an nucleoli in the nucleus, composed of:
proteins(enzymatic activity), metabolites, and ions.
When its nucleic acids and other soluble component are removed, forming (nucleoskeleton)

27. Genetic effects in nuclear envelpoe
Genetic effects in nuclear envelope proteins are known to cause at least 14 disorders, including muscular dystrophies, lipodystrophies, and neruropathies ( 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.