DNA Replication Process

BioCodeKb - Bioinformatics Knowledgebase

Genetic material must be able to be accurately replicated and passed on from one generation to the next. Although elegant experiments showed that DNA could carry genetic information from one generation to the next, not until Watson and Crick discovered the structure of DNA was it understood how DNA might be replicated. The double-helical model of DNA suggested that the strands can separate and act as templates for the formation of a new, complementary strand. However, the structure of DNA did not reveal whether the DNA was replicated conservatively or semiconservatively but it is thought to be semiconservatively.


DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inheritance. The cell possesses the distinctive property of division, which makes replication of DNA essential.


During replication, the two complementary strands  are separated. Each strand of the original DNA molecule then serves as a template for the production of its counterpart, a process called semiconservative replication. As a result of semi-conservative replication, the new helix will be composed of an original DNA strand as well as a newly synthesized strand. Cellular proofreading and error-checking mechanisms ensure near perfect fidelity for DNA replication.


Some other proteins and enzymes, in addition the main ones above, are needed to keep DNA replication running smoothly. One is a protein called the sliding clamp, which holds DNA polymerase III molecules in place as they synthesize DNA. There are three main steps in DNA synthesis


Initiation

Replication begins at a location on the double helix known as “oriC” to which some initiator proteins bind and trigger unwinding. Enzymes known as helicases unwind the double helix by breaking the hydrogen bonds between complementary base pairs, while other proteins keep the single strands from rejoining. The “topoisomerase” proteins surround the unzipping strands and relax the twisting that might damage the unwinding DNA. The cell prepares for the next step, elongation, by creating short sequences of RNA called primers that provide a starting point of elongation.


Elongation

With the primer as the starting point for the leading strand, a new DNA strand grows one base at a time. The existing strand is a template for the new strand. The enzyme DNA polymerase controls elongation, which can occur only in the leading direction. The lagging strand unwinds in small sections that DNA polymerase replicates in the leading direction. The resulting small “Okazaki fragments” can contain 1,000 to 2,000 bases in bacteria, but eukaryotic organisms having cells with nuclei have fragments of only 100 to 200 bases. The fragments terminate in an RNA primer that is later removed so that enzymes can stitch the fragments into an elongating strand.


Termination

After elongation is complete, two new double helices have replaced the original helix. During termination, the last primer sequence must be removed from the end of the lagging strand. This last portion of the lagging strand is the telomere section, containing a repeating non-coding sequence of bases. Enzymes snip off a telomere at the end of each replication, leading to shorter strands after each cycle.


Termination requires that the progress of the DNA replication fork must stop or be blocked. Termination at a specific locus, when it occurs, involves the interaction between two components;

(1) a termination site sequence in the DNA

(2) a protein which binds to this sequence to physically stop DNA replication.


Finally, enzymes called nucleases “proofread” the new double helix structures and remove misaligned bases. DNA polymerase then fills in the gaps created by the excised bases.

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