R02.4: DNA Replication

DNA replication is of great importance to the cell, as a copy of the genome must be given to each daughter cell if cell division is to be successful. Replication is a highly accurate process that is similar in nearly all eukaryotic cells.

Initiation of Replication

Replication only occurs during the S phase of the cell cycle (synthesis phase); this is about 12 hours long in most cells, including malignant cells.

Process of Replication

Each daughter cell receives one side of the DNA strand; and replication involves splitting of the DNA into separate strands. Each strand then has nucleotides added to it to form two new strands of DNA. DNA polymerase, which adds nucleotides to a single strand of DNA, can only work in the 5' to 3' direction. The complementary strand for the 5' - 3' strand is created by DNA polymerase and immediately united with its template; the 3' - 5' strand is read 'in reverse' by DNA polymerase (5' - 3') as a 100 - 200 base 'Okazaki fragment', and then united to the 3' - 5' template separately.

Checking of Accuracy

There are several mechanisms in place to prevent errors in DNA replication.

  • The structure of DNA polymerase has highest affinity for the correct nucleotide, preventing the incorrect nucleotide from associating with it.
  • If the incorrect nucleotide is attached, this may be immediately recognised by DNA polymerase which can excise the error immediately
  • Mismatch repair proteins are able to sense errors in the DNA helix caused by incorrect insertion of nucleotides; these proteins target the abnormal strand at allow other proteins to excise the damage. An inherited defect of a single mismatch repair gene is the cause of hereditary non-polyposis colon cancer (HNPCC), due to the increased rate of mutations that occur when this system is poorly functioning.