DNA Replication

The Three Alternative Models

Initially to model DNA replication, was three alternatives, named Conservative, Semi-Conservative, and Dispersive (similar to political parties).

The Conservative Model had parental strands directly synthesize an entirely new double stranded model. The parental strands are fully "conserved" as namely so. 

The Semi-Conservative Model had two parental strands each making a copy of itself. After one round of replication, the two daughter molecules each have one parental and one new strand. 

The Dispersive Model had material in the two parental strands, dispersing randomly between the two daughter molecules. After one round of replication, the daughter molecules contain a random mix of parental and new DNA.

A table shown below, shows the visual model for each alternative. Notice key differences between first and second replications, connecting the process and significance of each model to unique attributes.

Which model is the most accurate? 

In 1954 Meselson and Stahl performed an experiment using bacteria. The bacteria was cultured with a heavy isotope N15, and transferred to a medium with N14 a light isotope. DNA was centrifuged and analyzed after each replication. 

Through further analysis of DNA samples after each generation, it became noticable that parental strands were following the Semi-Conservative Model. 

Step by Step in DNA Replication

1. First DNA replication begins at sites called origins of replication. Various proteins attach to the origin of replication and open the DNA to forma replication fork. (Think back to the zipper)

2. Helicase will unwind the DNA strands at each replication fork. To keep the DNA from re-bonding with itself proteins called single strand binding proteins (SSBPs) bind to the DNA to keep it open. Topoisomerase will help prevent strain ahead of replication fork by relaxing supercoiling.

3. The enzyme primase initiaties replication through the addition of short segments named RNA, called primers. (primase > primers easy to recognize) to the parental DNA strand. The enzymes that synthesize DNA can only attach new DNA nucleotides to an existing strand of nucleotides. Primers are the foundation for DNA synthesis to occur. 

4. Antiparallel elongation, is where DNA Polymerase (DNAP III) attaches to each primer on the parallel strand, thus moving in the 3' to 5' direction. 

As DNAP III moves it adds nucletodies to the new strand in the 5' to 3' direction. The DNAP III follows helicase is known as the leading strand, only requiring one primer. The DNAP III on the other parental strand moves away from helicase, is known as the lagging strand, requiring many primers. 

5. The leading strand is synthesized within one continous segment. Contraily, the lagging strand moves away from the replication fork, as it is synthesized within chunks. Okazaki fragments are segments of the lagging strand.

6. After DNAP III forms an Okazaki fragment, DNAP I then replaces RNA nucleotides with DNA nucleotides. This is done through the presence of DNA ligase, which joins the Okazaki fragments, continously forming a DNA strand.