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DNA Replication Mechanism and Proofreading

DNA replication is the process by which a cell makes exact copies of its DNA. This process occurs in all organisms and is essential to biological inheritance, cell division, and repair of damaged tissues. DNA replication ensures that each of the newly divided daughter cells receives its own copy of each DNA molecule. DNA most commonly occurs in double-stranded form, made up of two complementary strands held together by base pairing of the nucleotides comprising each strand. The two linear strands of a double-stranded DNA molecule typically twist together in the shape of a double helix.

Figures (8)

Formation of the Okazaki fragments
A circular chromosome, showing DNA replication proceeding bidirectionally, with two replication forks generated at the "origin". Each half of the chromosome replicated by one replication fork is called a "replichore". (Graphic computer art by Daniel Yuen)
DNA polymerase moves along the old strand in the 3'–5' direction, creating a new strand having a 5'–3' direction.
DNA polymerase with proofreading ability
A slight mutation in the matched nucleotides can lead to chromosomal aberrations and unintentional genetic rearrangement
Bidirectional replication in a circular chromosome.
oriC motifs in bacteria

Key Points

  • A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA.
  • The replication fork is a structure that forms within the long helical DNA during DNA replication.
  • The leading strand is continuously extended from the primer by a DNA polymerase with high processivity, while the lagging strand is extended discontinuously from each primer forming Okazaki fragments.
  • The lagging strand is the strand of new DNA whose direction of synthesis is opposite to the direction of the growing replication fork, although the chemical reaction is exactly the same.
  • Okazaki fragments are short sequences of DNA nucleotides (approximately 150 to 200 base pairs long in eukaryotes) which are synthesized discontinuously and later linked together by the enzyme DNA ligase to create the lagging strand during DNA replication.
  • Compared to other Family B polymerases, the DEDD exonuclease family responsible for proofreading is inactivated in Pol α.

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