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

860 Nucleic Acid Synthesis

may affect survival and predisposition to specific diseases require dissociation and reassociation of the nucleosome
in the long term. core.

G. Repetitive Sequences: Selfish DNA
II. NUCLEIC ACID SYNTHESES
Even before the precise genome sequences are elucidated,
one unique feature of the metazoan DNA sequence has A. Similarity of DNA and RNA Synthesis
been established from a number of studies. A large frac-
All nucleic acids are usually synthesized by DNA temp-
tion (perhaps up to 90% or more) of the total genomic
late-guided polymerization of nucleotides—ribonucl-
sequence in metazoan cells do not encode any informa-
eotides for RNA and deoxy(ribo)nucleotides for DNA.
tion. Some of these sequences are present as noncoding

The reactant monomers are 5 ribonucleoside (or deoxyri-
intervening regions in genes, named “introns,” which do
bonucleoside) triphosphates. These can be described in
not code for proteins. However, the intron sequences are
the following chemical equations:
transcribed but are removed during processing (“splic-
ing”) to generate mature mRNA, as discussed later. Many
DNA + ndNTP → DNA + nPP i
←
of the other genomic sequences are not even transcribed,
and these may often be present as multimeric repeats of and
shorter units. These repetitive sequences have no known
(DNA) + nNTP → (DNA) + RNA + nPP i .
←
function in the cell, yet are maintained and replicated as
an integrated part of the genome; such DNA is referred to Enzymatic polymerization is carried out by DNA and
as “selfish DNA.” RNA polymerases, both of which carry out pyrophos-
Metaphasechromosomesareorganizedinsubstructures phorolysis, i.e., cleavage of a high energy pyrophosphate
distinguished by their staining with dyes. Euchromatin bond coupled to esterification of 5 phosphate linked to

regions contain transcribed sequences, while heterochro- the 3 -OH of the previous residue. The reaction is re-

matin regions contain large segments of repetitive se- versible, although it strongly favors synthesis. Degrada-
quences. Metaphase chromosomes are also characterized tion of nucleic acids is not due to reversal of the reaction,
by specific stained sequences (named centromeres) in the but rather a hydrolytic reaction catalyzed by nucleases,
middle of the elongated structure, in addition to telomeres namely, RNases and DNases, which generate nucleotides
at the termini, as discussed earlier. Both centromeres and or deoxynucleotides, respectively.
telomeres have unique repetitive sequences, and in some Three distinct stages are involved in the biosynthesis of
cases similar sequences have been observed in other re- both DNA and RNA: initiation, chain elongation, and
gionsofchromosomes;theseregionsarehighlycondensed termination. Initiation denotes de novo synthesis of a
and not transcribed. nucleic acid polymer which is generally well regulated
by complex processes, as described later. The key differ-
ence in initiation of a DNA vs RNA chain is that RNA
H. Chromatin Remodeling and
polymerases can start a new chain, while all DNA poly-
Histone Acetylation
merases require a “primer,” usually a short RNA or DNA

InordertomaketheDNAtemplateavailableforbothrepli- sequence with a 3 -OH terminus, to which the first de-
cation and transcription, the chromatin is “remodeled.” oxynucleotide residue is added. Elongation denotes con-
One way to accomplish this reversible process is by alter- tinuing polymerization of the monomeric nucleotides, and
ing the electrostatic interaction with histone. Acetylation termination defines stoppage of nucleotide addition to the
of lysine residues (and to some extent phosphorylation of growing polymer chain.
serine and threonine residues) reduces the binding affin- During synthesis the enzymes catalyzing the polymer-
ity of histones with DNA in nucleosome cores and may ization reaction are guided by nucleic acid templates that
thus allow exposure of free DNA to the transcriptional provide the complementary sequence for the incorporated
machinery. Additionally, a more complex energy-driven nucleotides (Fig. 4). The basic catalytic enzyme in such
process involving the proteins SNF1 and SWI causes a ma- reactions is called DNA or RNA polymerase. In cells the
jor alteration of the chromatin structure, which is neces- template for both DNA and RNA is genomic DNA. There
saryforreprogrammingofthetranscriptionalregimendur- are some exceptions to these general rules. Some DNA
ing growth, development, and associated differentiation. polymerases can synthesize homo- or heteropolymers of
DNA replication also requires access of DNA in free form deoxynucleotides in vitro in the absence of a template;
to the replication machinery and, therefore, may also be the substrate is restricted to one or two dNTPs. While
dependent on the same remodeling process and could even it is unlikely that these homo- or heteropolymers, e.g.,