Replication and DNA Polymerization

INTRODUCTION

Before dividing into daughter cells, a cell first replicates its DNA. During this process, the parental DNA unwinds, and each strand of a double helix acts as a template for new DNA synthesis. Because the resulting DNA molecules consist of one parental, or conserved, strand and one new strand, DNA replication is referred to as semiconservative. The accompanying animations show DNA replication at two different levels: molecular and chromosomal.

ANIMATION SCRIPT

DNA Polymerization

DNA polymerases catalyze the synthesis of the new DNA strands from a DNA template.

DNA polymerases require a preexisting RNA or DNA strand, the primer, to initiate new DNA synthesis. These polymerases add deoxyribonucleotides only to the 3' end of a growing strand.

Taking a closer look at the nucleotide polymerization reaction, the 3' end of the primer contains a free 3'-hydroxyl group.

The 3' hydroxyl reacts with the 5' end of the next free nucleotide to be added.

Free nucleotides continue to be added to the growing DNA strand by the same type of reaction.

Overall, the new DNA strand grows in the 5'-to-3' direction.

Replication of a Chromosome

A eukaryotic chromosome contains a long, linear molecule of double-stranded DNA. This DNA is tightly coiled within the chromosome, but unravels during interphase, when DNA replication occurs. A eukaryotic chromosome contains multiple origins of replication.

At each origin of replication, DNA synthesis proceeds bidirectionally. Two replication forks move outward in opposite directions.

The replicating DNA helices from each origin elongate and eventually join each other.

The original chromosome has been replicated to form two identical daughter DNA molecules, also called sister chromatids.

CONCLUSION

A human cell spends an estimated eight hours replicating its DNA before dividing into two daughter cells. During this time, a thousand or more different origins of replication may open up to initiate the replication process. From the opening of each origin, two replication forks travel in opposite directions, adding nucleotides at an estimated rate of 100 base pairs per second. Bacteria replicate their DNA even faster, at rates as high as 1000 base pairs per second.

Despite these fast rates, DNA replication is surprisingly accurate. During the polymerization process, DNA polymerases proofread and correct virtually every mismatched nucleotide that they may incorporate into a new DNA strand. Other enzymes also contribute to the repair effort, ultimately leaving a cell with just one error in every billion new nucleotides. By investing energy in proofreading and repair mechanisms, cells protect the fidelity of their genetic information from one generation to the next.