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Encyclopedia of Physical Science and Technology en010k-502 July 16, 2001 16:56

Nucleic Acid Synthesis 861

FIGURE 5 Replication of mammalian viral RNA genome. The
basic steps of replication are shown for (A)a(+) strand genome,
FIGURE 4 Replication of circular DNA of prokaryotes and which acts as an mRNA for encoding viral proteins; (B)a(−) viral
viruses, plasmids, and mitochondria. The basic steps of replica- genome cannot encode protein and first has to be replicated by the
tion are shown. (A) Rolling circle mode of replication for single- RNA replicase (•) which is present in the virus particle. Once the
stranded circular DNA: single-stranded (ss) DNA is replicated to complementary (+) strand which serves as mRNA is synthesized,
the replicative form (RF), which then acts as the template for viral-specific proteins are synthesized, including RNA replicase.
progeny ssDNA synthesis via a rolling circle intermediate. (B) Cir- (C) Replication of (+) stranded retroviral genomes first involves
cular duplex DNA can be replicated at the ori site by formation of a synthesis of the reverse transcriptase which directs synthesis of
θ intermediate. Replication could be bidirectional (as shown here) duplex DNA in two stages from the RNA template. Circularization

or unidirectional. 5 → 3 chain growth dictates that DNA synthesis of the DNA followed by its genomic integration allows synthesis of
is continuous on one side of the ori and discontinuous on the other progeny viral RNA by the host transcription machinery.
side for each strand; (+) and (−) strands are shown to distinguish
the strand types. (C) Replication of a linear genome with multiple
origins. negative strand, which then serves as the template for syn-
thesis of the progeny positive strand RNA. The progeny
(dA•dT) n or poly(dA) n •poly(dT) n , are formed in vivo, the RNA is then packaged into mature progeny virus.
availability of these polymers significantly advanced our In contrast, the genomic RNA of negative strand
understanding of the properties of DNA, before the age of viruses (e.g., vesicular stomatitis virus) cannot function
chemical or enzymatic oligonucleotide synthesis. directly as mRNA and thus cannot guide synthesis of pro-
There are some exceptions to the norm of DNA- teins, including the RNA replicase, by itself after the in-
dependent DNA or RNA synthesis, mostly in lower fection of host cells. These viruses carry their own RNA
eukaryotes or viruses (Fig. 5). One example is RNA- replicase within the virion capsids, which carry out (+)
dependent RNA synthesis in plant, animal, or bacterial mRNA strand synthesis after infection (Fig. 5).
viruses. In these cases, a single-stranded RNA template Retroviruses comprise diverse groups of viruses, in-
rather than double-stranded DNA guides synthesis of the cluding human immunodeficiency virus (HIV), which
complementary RNA strand, based on conventional base share a common mechanism of genome replication.
pairing. The polarity of RNA adds a level of complex- The RNA genomes of these viruses encode an RNA-
ity during synthesis. Thus, the RNA genome of a virus dependent DNA polymerase (reverse transcriptase or
that can be directly read and thus provides the mRNA RT) which first generates the complementary (c) DNA of
function is called the positive strand, as in polio virus. In the viral genome. RT has also RNaseH (specific nuclease
this case, the viral genome RNA functions as the mRNA for degrading RNA from RNA–DNA hybrids) and DNA-
and encodes the RNA polymerase, which is synthesized dependent DNA polymerase activities. After copying the
like other viral proteins in the infected cell. This RNA RNA template, the enzyme degrades the RNA and is able
polymerase subsequently synthesizes the complementary to convert the resulting single-stranded cDNA to duplex