The Cell - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 11

5 ′

3 ′
Lagging strand

Okazaki fragment

3 ′

5 ′

Leading strand

Movement of replication fork

RNA primer

5 ′

3 ′

Figure 1.4 DNA replication—replication fork.

Finally, the broken ends are sealed by DNA ligase. Base excision repair mechanism
requires DNA glycolsylases that recognize specific deamination and remove the base
by cleaving the N -glycosyl bond, then repairing it using endonucleases. In some
cases where the whole nucleotide is excised, the distortion is repaired by making
cuts at a distance of a few base pairs from the lesion site and then resynthesizing
the DNA strand using DNA polymerase ε and ligating the two DNA pieces. In some
other cases like dimer formation, the lesion is corrected without excision. Other
cases may involve damage to the complementary strand itself, like double strand
breaks, crosslinks, or damages encountered on the replication fork. In a few such
cases, a recombinational repair system involving homologous chromosomes helps
in repair; otherwise, error-prone translesional DNA synthesis takes up the repair
responsibility. But the chances of mutation are very high in such cases as repair is
not very accurate [2-1] .

DNA Recombination
The sequence of genes present often is altered or changed due to continuous rear-
rangement mechanisms. These rearrangement mechanisms aid in the evolution/adap-
tation in response to changes in external environments. They also constitute a type
of specialized DNA repair system. The precise mechanism by which such rearrange-
ments take place is termed genetic recombination.
The basic recombination is homologous recombination, where the chromosomes
having regions with similar base pair sequences align near each other, and then
crossover takes place between chromatids. The double strands of DNA are broken,
and some of the nucleotides are digested by exonuclease activity. The cut ends seek a
similar region in the opposite strand and join there. This brings about branch migra-
tion and creates a crossover structure called Holliday intermediates. These Holliday
intermediates undergo cleavage to produce two recombination products ( Fig. 1.5 )