Interphase Nuclei: Structure and Function in Detail

Posted on Dec 8, 2024 in Biology

Interphase Nuclei: Concept and Structure

Concept

A separate structure from the cytoplasm by a membrane envelope that acts as the cell’s genetic memory.

Basic Structure

The basic structure enables us to distinguish the nuclear envelope, chromatin, nucleolus, and nucleoplasm.

1. Nuclear Envelope

Formed by two membranes separated by a perinuclear space, crossed by pores, the outer membrane has ribosomes on its outer surface. The nuclear envelope has, on the nucleoplasm side, a dense inner membrane called the nuclear lamina, which contains three major polypeptides, lamins A, B, and C. Its function is to support and strengthen the nuclear envelope.

  • Nuclear Pores: Each is limited by a disc-shaped structure known as the pore complex. The pore complex is composed of eight blocks organized in subunits: annular, lumen, spine, and ring. Each block has protein fibrils that protrude on both sides of the complex.
  • Annular Lamellae: In different cell types of the gonads, complexes identical to the nuclear pore membrane can be found in the cytoplasm, forming stacks called annular lamellae.

Transport Between the Nucleus and Cytoplasm: Functionally, small molecules diffuse rapidly through the pore complex. For the nucleus to incorporate large molecules, a transport mechanism is needed, which is carried out by nuclear import receptors that widen the pore. This requires the collaboration of nucleoporins, which allow the diaphragm to dilate, and a short signal peptide that is removed after penetration.

2. Chromatin

Components: Chromatin is the most abundant component of the nucleus and consists of DNA and proteins.

  • DNA: Comprising two nucleotide chains that together form a double helix around an axis. Each nucleotide consists of a sugar (a pentose) which covalently binds to a phosphate and a nitrogenous base. There are four bases: two purines (adenine and guanine) and two pyrimidines (cytosine and thymine). These bases establish hydrogen bonds that hold together the two chains of nucleotides. The base sequence must be complementary. This is the Watson-Crick model. For an organism, the amount of DNA per cell is constant and is a function of chromosomes. Functionally, DNA represents the molecule of heredity. The only variable region in both nucleic acids is the alternation in each molecule of the nucleobases present; this sequence of bases carries the genetic information. The human genome contains about 3 billion base pairs spread across 46 chromosomes. Genes are elements that contain the information that determines the characteristics of a species as a whole, as well as each of the individuals who compose them. Each gene is a nucleic acid sequence that encodes a functional polypeptide.

  • Protein: Can be classified into two groups:

    • Histones: Globular proteins, basically due to their high content of the amino acids arginine and lysine. There are five different types: H1, H2A, H2B, H3, and H4.
    • Nonhistone: Include:
      • Acidic Proteins: Nucleoplasmin binds histones H2A and H2B, and the N1 protein binds to histones H3 and H4. There are also acidic waste proteins in the nucleus.
      • Enzyme Proteins: Involved in functions performed by DNA.

Organization:

  • 10nm Fiber: The elements that are repeated in this structure are called nucleosomes and have a diameter of 10 nm. They are formed by a succession of nucleosomes in contact with one another. Each nucleosome consists of two molecules each of histones that associate to form an octamer surrounded by two turns of the DNA molecule. This is the model of the extended chromatin fiber.
  • 30nm Fiber: To show the existence of these fibers, the solenoid model is proposed, whereby the 10nm fiber is arranged as a spring helically around 30nm in diameter.
  • Chromatin in the Metaphase Chromosome: The chromatin that is widespread in the interphase nucleus has yet to be condensed about 100 times to form the chromosomes of dividing cells.

3. Nucleolus

Components: A structure devoid of a membrane, in which the fibrillar and granular components are distinguished.

Nucleolar Organizers: They are part of the nuclear chromatin whose DNA, called rDNA, contains multiple repeat genes coding for three of the four rRNA ribosomes.

Nuclear Functions

Replication

For any cell to divide, the DNA must be doubled so that the genetic information is transmitted to daughter cells. This is possible through DNA replication. It is a semiconservative process in which each strand acts as a template for the synthesis of new chains of nucleotides.

  • Mechanism of Replication: It starts where we find special sequences that act as initiation signals, the origins of replication. After the double helix is opened, the hydrogen bonds begin to break through the action of an enzyme, DNA helicase. The separation is maintained by the union of each DNA strand to the helix-destabilizing protein. In each replication origin, two brackets grow in opposite directions; DNA replication is bidirectional. The synthesis of the new chain of nucleotides is catalyzed by the enzyme DNA polymerase, which catalyzes the formation of a phosphodiester bond between the 3′-hydroxyl terminal of a nucleotide primer (an RNA called a nucleotide nitrogenous base) and the complementary nucleotide facing the chain that acts as a template. This DNA polymerase catalyzes the reaction such that chain growth occurs in the 5′ to 3′ direction. Because the strands are antiparallel, the synthesis of the chain whose template address is 3′-5′ is continuous, but the other is discontinuous (Okazaki fragments). The continuously synthesized chain is called the leading strand, and the discontinuous one is called the lagging strand. In the leading strand, only one RNA primer is needed, while in the lagging strand, an RNA primer is needed for each fragment. DNA synthesized on the lagging strand undergoes a folding pattern, forming a single complex so that the replication proteins can be used together in the replication of both strands. There are special proteins, topoisomerases, that prevent DNA tangling with the advancing replication fork. Topoisomerase 1 generates a transient break in a single strand, which allows both pieces to rotate independently of each strand. Topoisomerase 2 generates a transient break in both strands.

  • DNA Repair: DNA polymerase has a proofreading activity. Before adding a new nucleotide to the growing chain, it verifies if the last nucleotide added has a correct base pairing with the template strand. If not, the polymerase removes the unpaired nucleotide by cutting the phosphodiester bond just formed. The proofreading mechanism explains why DNA polymerase synthesizes DNA only in the 5′-3′ direction, despite the drawbacks of the replication fork mechanism. In the place where the replication machinery makes an error in the copy, there is an unpaired nucleotide. If not corrected, the mismatch will translate to a mutation. Affecting only a few nucleotides can destroy an organism if the change occurs in a vital position in the DNA sequence. The cell has a mechanism for repairing DNA mismatches. The importance of mismatch repair in humans was demonstrated when it was discovered that an inherited predisposition to certain cancers is caused by mutations in the gene responsible for the production of a mismatch repair system protein. Inheriting a damaged gene in the mismatch repair system predisposes an individual to cancer.

Transcription

Jacob and Monod postulated the need for the existence of a chemical intermediary between the nucleus and the cytoplasm, where protein synthesis occurs, elucidating the so-called central dogma of biology: DNA -> RNA -> protein. RNA synthesis is carried out by DNA transcription. Unlike DNA, RNA is formed by only one string of nucleotides, contains ribose instead of deoxyribose, and uracil instead of thymine.

  • Types of RNA:

    • Messenger RNA (mRNA): Consists of a long chain of nucleotides. It carries the information contained in the nuclear DNA to the cytoplasm regarding the order in which amino acids should be placed for the synthesis of a particular protein.
    • Transfer RNA (tRNA): Consists of a one-dimensional chain of nucleotides, a feature in its “cloverleaf” shape, which is important for the performance of its duties. tRNA identifies and transports amino acids to where protein synthesis takes place, the ribosomes.
    • Ribosomal RNA (rRNA): The fundamental constituent of ribosomes, which are the cellular organelles responsible for protein synthesis.

  • General Transcription Machinery: Best known in bacteria.

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