11-The Cell Nucleus

Overview of the Cell Nucleus

  • The cell nucleus is a membrane-enclosed organelle found in all eukaryotic cells.

  • Eukaryotic cells are defined by the presence of a nucleus, as the term 'Eukaryon' literally translates to 'true nucleus.'

  • Prokaryotic cells do not contain a cell nucleus or any other membrane-bound organelles.

  • The nucleus serves as the main organelle that controls the entire cell and facilitates cellular reproduction.

Primary Functions of the Nucleus

  • Physical Separation: It serves as a boundary physically separating DNA from the cytoplasm’s complex metabolic machinery using the nuclear membrane.

  • Command Center: It acts as the command center of the cell, controlling all cellular activities.

  • Genetic Storage: It contains the majority of the cell's DNA and genetic information, making it the most critical part of eukaryotic cells.

Components of the Nucleus

  • Nuclear Envelope: A double membrane that is riddled with pores.

  • Nuclear Pore: Supported by the Nuclear Pore Complex (NPC).

  • Nucleoplasm: The fluid interior portion of the nucleus.

  • Nucleolus: A dense cluster of RNA and proteins responsible for ribosome assembly.

  • Chromatin: The molecular structure of chromosomes, consisting of the total DNA and associated proteins.

The Nuclear Envelope (NE)

  • Structure: A double membrane consisting of space between two phospholipid bilayers.

  • Membranes: It consists of an Inner and Outer nuclear membrane with a perinuclear space between them.

  • Nuclear Lamina: The inner membrane is lined with a fiber network known as the nuclear lamina, which provides attachment sites for chromatin.

  • Outer Membrane: This membrane is continuous with the Endoplasmic Reticulum (ER) and is studded with ribosomes for protein synthesis.

  • Perinuclear Space: The space between the inner and outer membranes is continuous with the cisternae of the ER.

Nuclear Pores and the Nuclear Pore Complex (NPC)

  • Definition: Small cylindrical channels that allow direct contact between the cytosol and the nucleoplasm.

  • Density: The number of pores is dependent on cell type and metabolic activity.

  • Control: The complex structure controls the transport of key molecules.

  • NPC Structure:

    • Parallel Rings: Two rings forming the rim of a wheel structure, consisting of 88 subunits.

    • Spokes: 88 spokes extend from the rings toward a central wheel hub.

    • Central Granule: Acts as a transporter to move macromolecules across the nuclear envelope.

    • Anchor Proteins: These proteins extend from the rim into the perinuclear space.

    • Fibers: Fibers extend from the rings into the cytosol and nucleoplasm, forming a basket-like cage or "fish trap."

Transport Across the Nuclear Envelope

  • Import into Nucleus: Enzymes and proteins required for DNA replication and transcription must be imported from the cytoplasm.

  • Export from Nucleus: RNA and ribosomes required for protein synthesis must be exported to the cytoplasm.

  • Ribosome Assembly: Ribosomes are partially assembled in the nucleus as subunits (composed of RNA and protein). These subunits are then transported to the cytoplasm where they combine to form functional, mature ribosomes.

  • Passive Transport: Small molecules and ions move via passive transport through aqueous channels.

  • Permeability: The envelope is permeable to small molecules. Nucleoside triphosphates, required for DNA and RNA synthesis, diffuse freely through the pores.

The Nucleolus

  • Function: Known as the "ribosome factory," it is the site where rRNA is synthesized and processed.

  • Features: It is a large, prominent structure that lacks its own membrane.

  • Constituents:

    1. Fibrillar Component: Consists of DNA (unraveled chromatin loops) and the RNA component of ribosomes. The DNA carries genes for rRNA, and transcription occurs in these dense areas.

    2. Granular Component: Consists of rRNA molecules and proteins. This component forms the ribosomal subunits that are eventually exported to the cytoplasm.

  • Activity Levels: The size of the nucleolus correlates with cell activity. In cells with high protein synthesis rates, the nucleolus can occupy 2020% to 2525% of the nucleus.

  • During Cell Division:

    • During division, chromatin condenses into chromosomes, the nucleoli disappear, and rRNA and proteins are degraded.

    • After mitosis, chromatin uncoils and RNA synthesis resumes. Many tiny nucleoli become visible and fuse into one large nucleolus.

Molecular Structure of Chromatin and Chromosomes

  • Eukaryotic Chromosome Components:

    1. Nucleic Acids: DNA is the primary nucleic acid.

    2. Proteins:

    • Histones: Basic pH proteins that bind to and stabilize DNA. These include Core Histones (H2AH2A, H2BH2B, H3H3, and H4H4) and the Linker Histone (H1H1).

    • Non Histone proteins.

  • Chromatin Fiber: A mixture of DNA and proteins forming the basic structural unit of chromosomes.

  • Nucleosomes: The simplest packing structure of DNA, appearing as ellipsoidal beads joined by linker DNA.

    • Histone Octamer: Consists of 22 copies of each core histone (H2A,H2B,H3,H4H2A, H2B, H3, H4).

    • Core DNA: Approximately 146 bp146\,bp of DNA wrapped around the histone octamer.

    • Linker DNA: DNA located between histone octamers, ranging from 88 to 114 bp114\,bp.

Hierarchy of DNA Packing

  • DNA Double Helix: Measured at 2 nm2\,nm in width.

  • Beads-on-a-string: The chromatin form measured at 11 nm11\,nm.

  • Chromatin Fiber: A 30 nm30\,nm fiber consisting of packed nucleosomes.

  • Extended Chromosome: Section measured at 300 nm300\,nm.

  • Condensed Chromosome: Section measured at 700 nm700\,nm.

  • Mitotic Chromosome: The host mitotic chromosome structure measures 1400 nm1400\,nm.

  • Net Result: Each DNA molecule is packaged into a mitotic chromosome that is 10,00010,000-fold shorter than its extended length.

Chromatin Types and Chromosome Number

  • Euchromatin: Lightly staining regions observed during interphase and early prophase.

  • Heterochromatin: Densely staining regions; these parts do not always encode proteins and are typically found at the centromere and the tips of the chromosome.

  • Somatic Cells: Contain chromosomes in pairs (homologous), representing the diploid number (2n2n).

  • Sex Cells: Ovum and sperm contain the haploid number (nn).

  • Chromosome Numbers (2n2n) by Species:

    • Human: 4646

    • Dog/Poultry: 7878

    • Horse: 6464

    • Cattle/Goat: 6060

    • Sheep: 5454

    • Elephant: 5656

    • Cat/Pig: 3838

    • Mouse: 4040

    • Monkey: 4242

    • Buffalo: 4848

    • Camel: 7474

    • Donkey/Guinea pig: 6464

    • Fruit fly: 88

    • Frog: 2626

    • Indian muntjac deer: 66

    • Horse round worm: 22

    • Butterfly: 440440

Chromosome Morphology and Classification

  • Metaphase Features: Chromosomes appear as double structures with two parallel strands (sister chromatids) connected by a common centromere.

  • Chromosome Types:

    • Autosomes: Identical in size and shape within pairs.

    • Sex Chromosomes: Differ in size and shape within pairs.

  • Centromere: Governs chromosome shape; defines the shorter arm (pp) and the longer arm (qq). Functions include holding sister chromatids together and facilitating movement.

  • Major Morphological Types (Centromere Position):

    1. Telocentric

    2. Acrocentric

    3. Submetacentric

    4. Metacentric

Specialized Chromosomal Features

  • Telomeres: Distal regions at both ends of chromosomes. They prevent fusion between different chromosomes (forming a "hairpin" structure). Length is maintained by the telomerase enzyme and declines with age.

  • Satellite: A tiny terminal extension or "stacked piece." It produces a narrow constriction called the secondary constriction. Chromosomes with this feature are called "SAT chromosomes." In humans, 55 of 2323 pairs have satellites. They are not found in sheep, goats, pigs, or horses.

  • Nucleolar Organizer Region (NOR): Specific regions containing rRNA synthesis genes. The nucleolus attaches to the NOR, which is usually located at telomeric ends.

Chemical Structure of Nuclear DNA

  • Definition: Polymeric molecules made of monomeric units called nucleotides.

  • Nucleotide Components:

    1. Nitrogen-containing base: Purines and Pyrimidines.

    2. Pentose (5-carbon sugar): Deoxyribose for DNA; Ribose for RNA.

    3. Phosphate group.

  • Terminology:

    • Base + Pentose = Nucleoside.

    • Base + Pentose + Phosphate = Nucleotide.

Nitrogenous Bases

  • Pyrimidines:

    • Cytosine (C): Found in DNA and RNA.

    • Thymine (T): Found in DNA only.

    • Uracil (U): Found in RNA only.

  • Purines:

    • Adenine (A): Found in DNA and RNA.

    • Guanine (G): Found in DNA and RNA.

Pentose Sugars and Linkages

  • Pentose Types: Ribose and 22-Deoxyribose.

  • Bonding:

    • The base is joined covalently to the 1′1' carbon of the pentose via an N-glycosyl bond (at N−1N-1 for pyrimidines and N−9N-9 for purines).

    • The phosphate is esterified to the 5′5' carbon.

  • Backbone Structure: DNA and RNA strands are linked by phosphate-group "bridges." Specifically, the 5′5'-phosphate group of one nucleotide joins the 3′3'-hydroxyl group of the next, creating a phosphodiester linkage.

  • Polarity: Each linear strand has distinct 5′5' and 3′3' ends. By convention, sequences are written from 5′5' to 3′3' (e.g., 5′ GTATTGC 3′5'\text{ GTATTGC }3').

DNA Structure and Properties

  • Double Helix: Two strands held together by hydrogen bonds between specific pairs: AA pairs with TT (22 bonds), and CC pairs with GG (33 bonds).

  • Antiparallel Orientation: One strand runs 3′3' to 5′5' while the other runs 5′5' to 3′3'.

  • Coding vs. Template:

    • Template Strand: The strand copied during nucleic acid synthesis.

    • Coding Strand: The strand that matches the RNA transcript encoding the protein.

  • Melting Point: DNA rich in G−CG-C pairs has a higher melting temperature than DNA rich in A−TA-T pairs.

  • Renaturation: Separated DNA strands will renature under physiological temperature and salt conditions at a rate dependent on concentration.

  • Grooves: Major and minor grooves wind parallel to the phosphodiester backbones and are critical for molecular interactions.