THE NUCLEUS

THE NUCLEUS
The nucleus is the headquarters of the cell. It is the most obvious organelle in any eukaryotic cell and appears as a large dark spot in EUKARYOTIC cells. It controls all cell activity.

The Nucleus is a membraneenclosed organelle which house most of the genetic information and regulatory machinery.

FUNCTIONS 1. It stores the cell's hereditary material, or DNA. 2. Site of DNA replication 3. Site of DNA transcription to mRNA 4. Ribosomal formation - Nucleolus: RNA & protein required for ribosomal synthesis 5. It coordinates the cell's activities, which include growth, intermediary metabolism, protein synthesis, and cell division by regulating gene expression

STRUCTURE The contents of the nucleus are enclosed by a complex nuclear envelope. Included within the nucleus are: 1- Chromatin 2- Nucleoplasm 3- Nucleolus (concentrated area of chromatin, RNA and proteins)

nuclear envelope nucleolus nuclear pores

chromatin

The NUCLEAR ENVELOPE The nuclear envelope completely encloses the nucleus and separates the cell's genetic material from the surrounding cytoplasm, serving as a barrier to prevent macromolecules from diffusing freely between the nucleoplasm and the cytoplasm.

The NE consists of two cellular membrane, an inner and an outer membrane, arranged parallel to one another and separated by 10 to 50 nanometers (nm).

The outer nuclear membrane is continuous with the membrane of the rough endoplasmic reticulum (RER). The space between the membranes is called the perinuclear space or intermembrane space and is continuous with the RER lumen.

The inner surface of the NE is bound to a thin filamentous network (lamins polypeptides) called the nuclear lamina. It provides mechanical support to the NE and sites for attachment for chromatin fibers.

THE NUCLEAR PORE

The nuclear pores are the gateways across which movement of RNAs and proteins takes place between the nucleus and cytoplasm in both direction. Proteins synthesized in the cytoplasm cross the nuclear envelop to initiate replication and transcription of genetic material. Similarly, mRNA, tRNA and ribosomal subunits built in the nucleus cross through the nuclear pores to the cytoplasm.

 The pore is 100 nm in total diameter and consists of around 100 proteins which allows the free passage of small water-soluble molecules while preventing larger molecules, such as DNA and proteins.

The nucleus of a typical mammalian cell has about 3000 to 4000 pores throughout its envelope.

nucleus

nuclear pores

Each pore contains a donut-shaped, eightfold, ring shaped structure at a position where the inner and outer membranes fuse. Attached to the ring is a structure called the nuclear basket that extends into the nucleoplasm, and a series of filamentous extensions that reach into the cytoplasm. Both structures serve to mediate binding to nuclear transport proteins.

Nuclear Transport
The entry and exit of large molecules to or from the cell nucleus is tightly controlled by the nuclear pore complexes.

Low molecular weight solutes Diffuse freely Macromolecules Regulated Protein import to nucleus Nuclear localization signal (NLS)

Protein involved in nuclear transport

Although small molecules can enter the nucleus without regulation, macromolecules such as RNA and proteins require association with karyopherins receptors :

1. Importins Cytoplasm to nucleus 2. Exportins Nucleus to cytoplasm

Import example - nucleoplasmin Step 1. Protein containing NLS binds soluble NLS receptor importin at the cytoplasmic side Step 2 Importin:NLS protein complex transports to cytoplasmic filaments

Step 3. Cytoplasmic filaments bend toward nucleus Step 4. Change in conformation of transporter Step 5. Inside the nucleus, Importin:NLS protein complex interaction with Ran-GTP causes a conformational change in the importin that causes dissociation

Nuclear Export
Nuclear export roughly reverses the import process; in the nucleus, the exportin binds the cargo and Ran-GTP and diffuses through the pore to the cytoplasm, where the complex dissociates.

NUCLEOPLASM
The nucleoplasm is a highly viscous liquid that surrounds the chromosomes and nucleoli. Nucleotides and enzymes are dissolved in the nucleoplasm.

NUCLEOLUS
:
The prominent structure in the nucleus is the nucleolus. It produces ribosomes, which move out of the nucleus and take positions on the ER (rough) where they are involve in protein synthesis.

CHROMATIN
Chromatin is the complex of DNA and protein (histones) found in the eukaryotic nucleus, that makes up chromosomes. The structure of chromatin varies significantly between different stages of the cell cycle, according to the requirements of the DNA

chromatin

chromosome

Single chromosome can only be visible during M phase

Based on the position of their centromeres, chromosomes are assigned a long arm and a short arm. The shorter arm of the chromosome is known as the p, or petite arm, from the French word for "small." The longer arm is known as the q, or queue arm, from the word meaning a line of people.

P arm centromere

Q arm

In the International System for Cytogenetic Nomenclature (ISCN) scheme, the numbering system for a chromosome begins at its centromere. Chromosomal regions that are present on the short arm will begin with the designation p, whereas regions on the long arm will begin with q. The regions are named p1, p2, etc., on the short arm and q1, q2, etc., on the long arm. The numbers assigned to each region get larger as the distance from the centromere to the telomere increases.

The packaging of DNA into chromosomes involves several orders of DNA coiling and folding.

The packaging of DNA into chromosome includes histone proteins and non histone proteins

The 30 nm chromatin fibers gather into larger supercoiled loops of thick fibers which are attached to a protein scaffold. Each of these loops contains approximately 100 kb of DNA.

TYPES OF CHROMATIN
In non-dividing cells there are two types of chromatin euchromatin and hetrochromatin. Euchromatin: is a lightly packed form of chromatin that is rich in gene concentration, and is often under active transcription. It is found in both eukaryotes and prokaryotes.

Hetrochromatin: Heterochromatin is a tightly packed form of DNA. Heterochromatin is inactive and remains compact during interphase. Hetrochromatin plays a role in gene regulation and the protection of the integrity of chromosomes, attributed to the dense packing of DNA, which makes it less accessible to protein factors that bind DNA or its associated factors.