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DNA, Chromosomes, DNA Replication and DNA Repair

Introduction to DNADNA (Deoxyribonucleic Acid) is a long molecule that contains the unique genetic code for all living organisms and many viruses. It plays a vital role in heredity, coding for proteins, and guiding the development and functioning of life.

Structural Features of DNA

• Double Stranded: DNA forms a stable double helix, which is crucial for its function as a genetic blueprint.

• Antiparallel Strands: The two strands of the helix run in opposite directions; one runs 5' to 3' and the other runs 3' to 5'.

• Right-Handed Helix: The helical structure twists in a right-handed manner, which is essential for compacting the DNA.

• Backbone: Made up of alternating sugar (deoxyribose) and phosphate groups, providing structural integrity.

• Base Pairing: Nucleotide bases (Adenine with Thymine and Guanine with Cytosine) bond through hydrogen bonds, creating the rungs of the ladder structure and allowing for complementary base pairing necessary for replication.

• Grooves: Major and minor grooves on the helix surface provide binding sites for proteins that regulate gene expression, replication, and repair.

Chromosomal DNA Organization

• Circular Chromosomal DNA: In prokaryotes, DNA is typically a single circular chromosome, which is simpler in structure compared to eukaryotic chromosomes.

• Supercoiling: In bacteria, DNA compacts through supercoiling, where the DNA twists upon itself. For instance, E. coli's chromosome can measure about 1200 micrometers, whereas human chromosomes range from 19,000 to 73,000 micrometers in length. This compact structure is vital for fitting into the confined space of the cell nucleus.

Eukaryotic Chromosomes

• Complex Structure: Eukaryotic chromosomes are composed of a complex of DNA and proteins known as chromatin, which can range into hundreds of millions of base pairs.

• Chromatin Configuration: Chromatin is condensed during mitosis into visible chromosomes, while during interphase, it is less condensed, allowing for gene expression and DNA replication.

• Nucleosome Formation: Eukaryotic DNA wraps around a core of histone proteins, forming nucleosomes, which looks like "beads on a string" and plays a critical role in regulating gene accessibility.

DNA Replication

• Basic Rules: DNA replication is semi-conservative, meaning that each new DNA molecule consists of one original and one newly synthesized strand. The strands are synthesized in the 5' to 3' direction and include both leading and lagging strands due to the antiparallel nature of DNA.

• Origin of Replication: This is a specific sequence where DNA replication begins, creating a replication bubble that expands as the process continues.

• DNA Polymerase: This enzyme synthesizes the new DNA strands by adding nucleotides complementary to the template strand and has proofreading capabilities to correct mismatches.

Key Proteins in DNA Replication

• DNA Helicase: Unwinds the double-stranded DNA at the replication fork, allowing access for other proteins and enzymes.

• Topoisomerase: Relieves the torsional strain that builds up ahead of the replication fork as DNA unwinds.

• Single-Strand Binding Proteins: Stabilize the unwound, single strands of DNA during replication to prevent them from re-annealing or forming secondary structures.

• Ligase: Joins the Okazaki fragments on the lagging strand, sealing nicks in the sugar-phosphate backbone and completing the continuous DNA strand.

DNA Repair Mechanisms

• Mutation: Any change in the DNA sequence can affect genes and may lead to various diseases, including cancer.

• DNA Damage Causes: Damage can arise from endogenous factors (like reactive oxygen species) and exogenous factors (such as UV radiation or chemicals).

• Repair Mechanisms:

  • Base Excision Repair: Corrects small, non-helix-distorting base lesions by removing the damaged base and replacing it with the correct one using DNA polymerase.

  • Nucleotide Excision Repair: A repair system that recognizes bulky distortion in the DNA, excises a segment of the strand containing the damage, and fills in the gap using DNA polymerase.

  • Mismatch Repair: Corrects errors that occur during DNA replication by identifying and repairing mismatched bases to ensure fidelity in DNA replication.

ConclusionUnderstanding the structure, replication, and repair of DNA is crucial for comprehending genetic functions and the mutations that can lead to diseases, enhancing our knowledge in fields such as genetics, medicine, and biotechnology.