Biotechnology and Bioinformatics (1+1)

1.4.2. Origins of a replication

For a cell to divide, it must first replicate its DNA. This process is initiated at particular points within the DNA, known as "origins", which are targeted by protein s that separate the two strands and initiate DNA synthesis. Origins contain DNA sequence s

recognized by replication initiator proteins (e.g.dnaA in E coli and the Origin Recognotion Complex in yeast).

These initiator proteins recruit other proteins to separate the DNA strands at the origin, forming a bubble.

Origins tend to be "AT-rich" (rich in adenine and thymine bases) to assist this process, because A-T base pairs have two hydrogen bonds (rather than the three formed in a C-G pair)—strands rich in these nucleotide s are gene rally easier to separate due to the positive relationship between the number of hydrogen bonds and the difficulty of breaking these bonds.

Once strands are separated, RNA primer s are created on the template strands.

More specifically, the leading strand receives one RNA primer per active origin of replication while the lagging strand receives several; these several fragments of RNA primers found on the lagging strand of DNA are called Okazaki fragments, named after their discoverer.

DNA polymerase extends the leading strand in one continuous motion and the lagging strand in a discontinuous motion (due to the Okazaki fragments).

RNase removes the RNA fragments used to initiate replication by DNA Polymerase, and another DNA Polymerase enters to fill the gaps.

When this is complete, a single nick on the leading strand and several nicks on the lagging strand can be found. Ligase works to fill these nicks in, thus completing the newly replicated DNA molecule.

As DNA synthesis continues, the original DNA strands continue to unwind on each side of the bubble, forming two replication forks . In bacteria, which have a single origin of replication on their circular chromosome, this process eventually creates a " theta structure " (resembling the Greek letter theta: θ). In contrast, eukaryotes have longer linear chromosomes and initiate replication at multiple origins within these.