DNA Polymerase

About DNA Polymerase:

DNA polymerase is an enzyme that synthesizes DNA molecules from deoxyribonucleotides, which are the building blocks of DNA. The enzymes play an essential role in DNA replication, usually working in pairs to produce two matching DNA stranges from a single DNA molecule. DNA polymerase creates two new strands that are identical to those that already exist. DNA polymerase adds nucleotides to the three prime end of a DNA strand one nucleotide at a time. When a cell divides, DNA polymerases are needed so that the cell's DNA can duplicate. It allows a copy of the original DNA molecule to be passed to each new cell.

DNA Polymerase Function
When DNA polymerase synthesizes DNA from deoxyribonucleotides, nucleotides are paired to bases on each strand of the original DNA molecule to create DNA copies. The pairings are always the same, with cytosine together with guanine, and thymine together with adenine. DNA polymerases cannot form new chains, they can only add a nucleotide to a pre-existing 3'-OH group. This means that they require a primer to add the first nucleotide. Primers consist of either RNA or DNA bases, but can also have both. When DNA is replicated, the first two bases are always RNA. Another enzyme, primase, synthesizes them, while helicase and topoisomerase II unwind DNA to turn it from a single string to a double strand.

DNA Polymerase Mechanism
DNA polymerase can make mistakes in its functioning; about one for every billion base pairs that are copied. However, some DNA polymerases can correct errors in newly-synthesized DNA. They do this by moving backwards by one base pair of DNA when an incorrect base pair is recognized. The correct base can be re-inserted by the polymerase so that the replication can keep going. This allows for the integrity of the DNA strand to be preserved so that it can be passed onto the daughter cells.
Many polymerases can detect base pair mismatches due to their exonuclease domain, which also helps to remove incorrect nucleotides and replace them with correct ones. This helps to prevent mismatches in DNA base pairing, which can cause dysfunctional proteins and cancer. Hydrogen bonds are important in base pair binding and interaction. When there is a mismatch and a loss of interaction occurs, the balance is disturbed, disrupting the binding of the template-primer from the polymerase to the exonuclease domain. DNA polymerization is also slowed down when the wrong nucleotide is incorporated. This leads to the DNA switching from the polymerase site to the exonuclease site.

DNA Polymerase Structure
The overall catalytic subunits of DNA polymerases do not differ much between species and are independent of domain structures. They have a conserved structure, which usually suggests a vital function in the cell that cannot be replaced. Its form is sometimes described as a right hand, which has thumb, finger and palm domains. The palm domain appears to catalyze the transfer of phosphoryl groups in the phosphoryl transfer reaction, while the finger domain binds the nucleoside triphosphates with the template base. The thumb domain might contribute to processivity, translocation, and positioning of the DNA.