Polymer of Nucleotides: DNA, or deoxyribonucleic acid, consists of long chains made up of repeating units called nucleotides. Each nucleotide is fundamental for genetic coding and ultimately determines the characteristics of living organisms.
A) Nitrogenous Bases
There are two categories of nitrogenous bases present in nucleotides:
Purines:
Adenine (A): One of the two purines in DNA, plays a key role in forming the base pairs with thymine.
Guanine (G): The other purine, pairs with cytosine, and is involved in various biochemical processes within the cell.
Pyrimidines:
Cytosine (C): Pairs with guanine, integral for maintaining the structure of DNA.
Thymine (T): The pyrimidine that pairs with adenine in DNA (Uracil (U) replaces thymine in RNA).
B) Nucleoside
A nucleoside is formed from a pentose sugar and a nitrogenous base, and it does not include a phosphate group.
Composed of:
Pentose sugar (ribose in RNA or deoxyribose in DNA) + nitrogenous base
Examples:
Adenosine: Formed from adenine + ribose, it is crucial in cellular energy transfer.
Cytidine: Formed from cytosine + ribose, it’s important in RNA structure.
C) Nucleotide
A nucleotide is the building block of DNA and RNA, composed of a pentose sugar, a nitrogenous base, and a phosphate group.
Composed of:
Pentose sugar + nitrogenous base + phosphate group
Energy Storage:
The energy harnessed from nucleotides is stored in the high-energy phosphate bonds, crucial for DNA synthesis and cellular processes.
Examples include:
dATP, dCTP, dGTP, dTTP: Nucleotides for DNA synthesis.
AMP, ADP, ATP: Critical for energy transfer and cellular respiration.
D) DNA Structure
DNA has a distinct double-helix structure that is vital for its functions.
Double-Stranded and Antiparallel:
The two strands run in opposite directions, with one strand oriented from 5' to 3' and the other from 3' to 5', allowing for replication and transcription.
Complementary Base Pairing:
Adenine pairs with thymine using two hydrogen bonds (A:::T)
Guanine pairs with cytosine using three hydrogen bonds (G:::C), enhancing stability.
Hydrogen Bonds:
The strands are held together by hydrogen bonds between the nitrogenous bases, providing the structure necessary for the genetic code.
E) DNA Packaging
DNA is negatively charged and is tightly packed with proteins called histones to form nucleosomes, which resemble beads on a string. This organization is crucial for fitting DNA into the nucleus.
Chromatin Structure:
Nucleosomes further coil and fold to form chromatin, which helps regulate gene expression and DNA replication.
DNA Polymerization
A) Requirements for DNA Replication
Precursors: - dNTPs (deoxynucleotide triphosphates) are the building blocks.
Energy: - Inherent energy in dNTPs powers strand synthesis.
Enzymes:
Helicase: Unwinds the DNA double helix, allowing access to the template strand.
Primase: Synthesizes short RNA primers that are necessary for DNA polymerases to begin synthesis.
DNA Polymerase: Adds complementary nucleotides to the growing DNA strand, maintaining accuracy through base pairing rules.
DNA Ligase: Joins Okazaki fragments on the lagging strand to create a continuous DNA strand.
Template: - The original DNA strand serves as a template for creating a new strand.
RNA Primer: - A short segment of RNA nucleotides, 5-17 bases long, is essential for initiating DNA synthesis.
B) Semi-conservative Model of DNA Replication
Each new DNA molecule consists of one old strand and one newly synthesized strand, ensuring genetic fidelity.
Leading Strand:
Synthesized continuously towards the replication fork.
Lagging Strand:
Synthesized in short fragments known as Okazaki fragments, which are later joined together.
Requires multiple RNA primers for synthesis.
Proofreading Mechanisms
DNA polymerase has proofreading capabilities to ensure accuracy in DNA replication.
Initial Error Rate: Approximately 1 in 100,000 bases can be incorrectly incorporated.
Proofreading Efficiency: The error rate is substantially reduced to 1 in 10 billion bases due to enzymatic proofreading mechanisms.
Mismatch Repair: Errors detected during replication are corrected by the replication complex, ensuring fidelity.
Excision Repair: Damaged or incorrectly paired bases are excised, and the appropriate bases are incorporated by DNA polymerase for repair.
Telomeres
Definition: Repeated DNA sequences at the ends of chromosomes, which protect them from deterioration or fusion with neighboring chromosomes.
Function: Vital for maintaining chromosomal integrity and influencing the lifespan of cell divisions.
Telomerase: An enzyme that adds repetitive sequences (e.g., TTAGGG) to the ends of chromosomes, active in stem cells and germ cells, and often found at elevated levels in cancer cells, facilitating their ability to proliferate indefinitely.