14.7 Molecular Mechanisms

197

Table 14.4 DNA replication

Name

Operand

Operation

Operator

Result

Premelting

Double helix

Facilitation

Topoisomerase

Strand separation

Melting

Double helix

Facilitation

Helicase

Strand separation

Synthesis

Single strand

Nucleotide

addition

Polymerase

Semiconserv-

atively replicated

double helix

Two DNA polymerases are simultaneously active. They catalyse template-directed growth in the

5 prime right arrow 3 prime5^' →3^' direction. The leading strand is synthesized continuously from 5 prime right arrow 3 prime5^' →3^' using the strand

beginning with the 3 prime3^' end as the template, whereas the lagging strand is synthesized in short

(“Okazaki”) fragments using the strand beginning with the 5 prime5^' end as the template. A DNA pri-

mase produces a very short RNA primer at the 5 prime5^' end of each Okazaki fragment onto which the

polymerase adds nucleotides. The RNA is then removed by an RNAase H enzyme. A DNA ligase

links the Okazaki fragments. A set of initiator proteins is also required to begin replication at the

origin of replication. This is, of course, a simplification; for example, it is estimated that almost 100

(out of a total of approximately 6000) genes in yeast are used for DNA replication, and another 50

are used for recombination

Table 14.5 Some types of chromosome rearrangements (with examples)

Name

BeforeSuperscript normal a^a

AfterSuperscript normal a^a

Deletion

ABCDEFGH

ABEFGH

Insertion

ABCDEFGH

ABCJFKDEFGH

Inversion

ABCDEFGH

ABCFEDGH

Transposition

ABCDEFGH

ADEFBCGH

Tandem duplications

ABCDEFGH

ABCBCBCDEFGGGGGH

Superscript normal a^aEach letter represents a block of one or more base pairs

correcting codes (Sect. 7.6), the DNA repair proteins must first recognize the error and

then repair it. It is of primordial importance that DNA is organized into a double helix;

the antiparallel strand can be used to check and template-repair mistakes recognized

in the other strand. Instead of repair, apoptosis (death of a single cell; as opposed to

necrosis, death of many cells in a tissue) of the affected cell may occur. Concomitant

with the work of the specific error recognition and repair enzymes, the entire cell

cycle may need to be slowed to ensure that there is time for the repair work to be

carried out. The mending systems are also used to repair damage caused by external

factors (e.g., cosmic ray impact and oxidative stress).

The available mechanisms are essentially directed towards repairing single-site

errors; there is no special apparatus for eliminating gene duplications and the like.

On the other hand, it is not only base mismatches that need to be repaired. Alkylation

(methylation) damage could adversely affect gene expression, and there are enzyme

systems (oxidative demethylases and others) for repairing it.

Just as certain sequences are more prone to error than others, so are certain erro-

neous sequences more easily repaired than others. While the quality of a telephone

line is, essentially, independent of the actual words being said, the fidelity of DNA

replication may be sequence-dependent. This possibility could be used by the genome