Replication of DNA

DNA is the only molecule in a cell able to duplicate itself without information from some other cell component. In contrast, as we have seen, RNA can only be formed using the information present in DNA, protein formation uses the information in mRNA, and all other molecules use protein enzymes to determine the structure of the products formed.

DNA replication is, in principle, similar to the process whereby RNA is synthesized. During DNA replication (Figure 5-11), the two strands of the double helix separate, and each exposed strand acts as a template to which free deoxyribonucleotide triphos-phates can base-pair, A with T and G with C. An enzyme, DNA polymerase, then links the free nu-cleotides together at a rate of about 50 nucleotides per second as it moves along the strand, forming a new strand complementary to each template strand of DNA. The end result is two identical molecules of DNA. In each molecule, one strand of nucleotides, the template strand, was present in the original DNA molecule, and one strand has been newly synthesized.

This description of DNA synthesis provides an overview of the basic elements of the process, but the individual steps are considerably more complex. A number of proteins in addition to DNA polymerase are required. Some of these proteins determine where along the DNA strand replication will begin, others open the DNA helix so that it can be copied, while still others prevent the tangling that can occur as the helix unwinds and rewinds.

A special problem arises as the replication process approaches the end of the DNA molecule. The complex of proteins that carry out the replication sequence is in part anchored to a portion of the DNA molecule that lies ahead of the site at which the two strands separate during replication. If a DNA molecule ended at the very end of the last gene, this gene could not be copied during DNA replication because there are no more downstream sites to anchor the replication complex.

This problem is overcome by an enzyme that adds to the ends of DNA a chain of nucleotides composed of several hundred to several thousand repeats of the six-nucleotide sequence TTAGGG. This terminal repetitive segment is known as a telomere, and the enzyme that catalyzes the formation of a telomere is

Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition

PART ONE Basic Cell Functions

Separated Polynucleotide Strands

FIGURE 5-11

Replication of DNA involves the pairing of free deoxyribonucleotides with the bases of the separated DNA strands, giving rise to two new identical DNA molecules, each containing one old and one new polynucleotide strand.

FIGURE 5-11

Replication of DNA involves the pairing of free deoxyribonucleotides with the bases of the separated DNA strands, giving rise to two new identical DNA molecules, each containing one old and one new polynucleotide strand.

telomerase. In the absence of telomerase, each replication of DNA results in a shorter molecule because of failure to replicate the ends of DNA.

Cells that continue to divide throughout the life of an organism contain telomerase, as do cancer cells and the cells that give rise to sperm and egg cells. The presence of telomerase allows cells to restore their telo-meres after each cell division, thus preventing shortening of their DNA. However, many cells do not express telomerase, and each replication of DNA leads to a loss of coded genetic information. It is hypothesized that the telomeres serve as a biological clock that sets the number of divisions a cell can undergo and still remain viable.

In order to form the approximately 40 trillion cells of the adult human body, a minimum of 40 trillion individual cell divisions must occur. Thus, the DNA in the original fertilized egg must be replicated at least 40 trillion times. Actually, many more than 40 trillion divisions occur during the growth of a fertilized egg into an adult human being since many cells die during development and are replaced by the division of existing cells.

If a secretary were to type the same manuscript 40 trillion times, one would expect to find some typing errors. Therefore, it is not surprising to find that during the duplication of DNA, errors occur that result in an altered sequence of bases and a change in the genetic message. What is amazing is that DNA can be duplicated so many times with relatively few errors.

A mechanism called proofreading corrects most errors in the base sequence as it is being duplicated and is largely responsible for the low error rate observed during DNA replication. If an incorrect free nu-cleotide has become temporarily paired with a base in the template strand of DNA (for example, C pairing with A rather than its appropriate partner G), the DNA polymerase somehow "recognizes" this abnormal pairing and will not proceed in the linking of nu-cleotides until the abnormal pairing has been replaced. Note that in performing this proofreading, the DNA polymerase needs to identify only two configurations, the normal A-T and G-C pairing; any other combination halts polymerase activity. In this manner each nucleotide, as it is inserted into the new DNA chain, is checked for its appropriate complementarity to the base in the template strand.

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Responses

  • dante
    Why can rna not be duplicated?
    8 years ago
  • Miia
    What problem is overcome by dna replication?
    8 years ago
  • Carlos
    What part of dna is actually copied during replication?
    8 years ago
  • Fergus
    Where in body where DNA replicates?
    7 years ago
  • eden eyob
    How deoxyribonucletides formed in the body?
    7 years ago

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