Makindo Medical Notes

Related Subjects: |DNA and RNA short notes |DNA replication |DNA structure in Nucleus |Mitosis and Meiosis |Cell Cycle

DNA replication is the biological process by which a cell makes an identical copy of its DNA. This process is essential for cell division, allowing each daughter cell to receive an exact copy of the parent cell's genetic material. DNA replication is highly regulated and involves a complex set of enzymes and other proteins to ensure accuracy and fidelity.

Key Concepts of DNA Replication

• Semi-Conservative Replication:
  • Each of the two daughter DNA molecules consists of one original (parental) strand and one newly synthesized strand.
• Replication Origin:
  • DNA replication begins at specific locations called origins of replication.
  • In prokaryotes, there is typically a single origin of replication, while eukaryotes have multiple origins on each chromosome.
• Replication Fork:
  • The replication fork is the Y-shaped structure where the DNA double helix is unwound, and new strands are synthesized.

Steps of DNA Replication

• Initiation:
  • Replication begins at the origin of replication, where specific initiator proteins bind to the DNA and unwind the double helix.
  • Helicase unwinds the DNA strands, creating a replication fork.
  • Single-strand binding proteins (SSBs) stabilize the unwound DNA strands and prevent them from re-annealing.
  • Primase synthesizes a short RNA primer complementary to the DNA template to provide a starting point for DNA synthesis.
• Elongation:
  • DNA polymerase III (in prokaryotes) or DNA polymerase δ and ε (in eukaryotes) extend the RNA primer by adding nucleotides complementary to the template strand.
  • DNA synthesis occurs in the 5' to 3' direction, meaning new nucleotides are added to the 3' end of the growing strand.
  • The leading strand is synthesized continuously, while the lagging strand is synthesized discontinuously in short fragments called Okazaki fragments.
  • Another DNA polymerase (DNA polymerase I in prokaryotes) removes the RNA primer and replaces it with DNA.
  • DNA ligase joins the Okazaki fragments to form a continuous DNA strand.
• Termination:
  • Replication continues until the entire molecule is copied.
  • In prokaryotes, termination occurs when replication forks meet, and the circular chromosome is separated.
  • In eukaryotes, replication ends when the replication machinery reaches the ends of the linear chromosomes.

Enzymes and Proteins Involved in DNA Replication

• Helicase:
  • Unwinds the DNA double helix at the replication fork.
• Single-Strand Binding Proteins (SSBs):
  • Stabilize the unwound DNA strands and prevent them from re-annealing.
• Primase:
  • Synthesizes short RNA primers to provide a starting point for DNA synthesis.
• DNA Polymerase:
  • Polymerase III (prokaryotes) or polymerases δ and ε (eukaryotes) add nucleotides to the growing DNA strand.
  • Polymerase I (prokaryotes) replaces RNA primers with DNA.
• DNA Ligase:
  • Joins Okazaki fragments on the lagging strand to create a continuous DNA molecule.
• Topoisomerase:
  • Relieves the tension in the DNA helix ahead of the replication fork by creating temporary nicks in the DNA.

Fidelity and Proofreading

• High Fidelity:
  • DNA replication is a highly accurate process, with an error rate of about 1 in 10⁹ to 10¹⁰ base pairs.
• Proofreading:
  • DNA polymerases have 3' to 5' exonuclease activity that allows them to remove incorrectly paired nucleotides.
  • Proofreading ensures the high fidelity of DNA replication by correcting errors during DNA synthesis.

Clinical Relevance

• Cancer:
  • Errors in DNA replication can lead to mutations, some of which may result in cancer if they affect genes involved in cell growth and division.
• Genetic Disorders:
  • Mutations in genes encoding DNA replication proteins can lead to genetic disorders, such as Bloom syndrome and Werner syndrome.
• Antibiotics and Chemotherapy:
  • Some antibiotics and chemotherapy agents target DNA replication machinery to inhibit bacterial growth or cancer cell proliferation.

Summary

DNA replication is a critical process that ensures the accurate transmission of genetic information during cell division. It involves the coordinated action of multiple enzymes and proteins to replicate the DNA double helix with high fidelity. Understanding the mechanisms and regulation of DNA replication provides insights into genetic stability, disease development, and therapeutic interventions.

DNA Structure

DNA Replication