The fidelity with which DNA is replicated is very high, so that the order of base pairs in each daughter DNA molecule is identical to the original parent duplex.

However, once replica­tion is completed, the normal structure of the DNA molecule may be altered, thereby producing a form that cannot readily be replicated.

For example, bases along one of the two strands may be chemically al­tered or removed entirely, adjacent bases along one strand may become linked together to form a dimer, or breaks may be introduced into one or both chains.

Such changes in the structure of a normal DNA mole­cule may not only interfere with proper replication but also change normal recombination events and pro­duce useless transcription products.

Several DNA repair mechanisms that can correct errors present in one or both strands of a molecule have been shown to exist in cells. Among these are ex­cision repair and post replication repair. Excision re­pair (Fig. 21-16), a DNA repair mechanism that has been demonstrated in both prokaryotes and eukaryotes, corrects for the presence of pyrimidine dimers within a strand.

Excision repair of a DNA Molecule in which One Strand contains a Pyrimidine Dimer

Such dimers are produced, for exam­ple, when DNA is exposed to ultraviolet radiation. P. Howard-Flanders, D. Pettijohn, P. Hanawalt, and oth­ers have shown that the nucleotides forming the dimer are enzymatically excised and the resulting gap in the strand then filled by the action of DNA polymerase I.

The repair enzyme nicks the defective strand at the 5′ end of the damaged region, following which DNA po­lymerase I bind at the nick and adds the appropriate complementary nucleotides to the free 3′ end. After adding a succession of nucleotides, the DNA poly­merase produces a second nick in the strand, releasing a short polynucleotide that contains the dimer. After this, DNA ligase closes the nick, thereby completing the repair process.

If a segment of one of the two strands of a double helix contains a dimer, then during replication the complementary strand that is synthesized will lack several nucleotides in that vicinity of the chain corre­sponding to the position of the dimer (Fig. 21-17); thus, the new strand has a gap in it and the original (defective) strand is single stranded in the region of the dimer.

Postreplication Repair of a DNA Molecule in which the Presence of a Dimer in One Original Strand Results in a Gap in the Newly Synthesized Complementary Strand

Such an error cannot be corrected by exci­sion repair, but is corrected by postreplieation repair. In postreplieation repair, the normal duplex is nicked and a repair enzyme realigns the single-stranded re­gion with the complementary region of the sister du­plex (i.e., the repair enzyme switches the free end of the nicked strand into the gap). The result is a cross- strand exchange.

Examination of the process de­picted in Figure 21-17 reveals that the upper hetero-duplex can now be repaired by the action of DNA polymerase I. However, we are still left with two dou­ble helices that are cross-stranded. Another repair en­zyme produces two nicks in the cross-stranded helices and recombines the free ends to produce two double helices that are no longer cross-stranded. The original dimer, which is now part of the lower double helix, can be corrected by the excision repair enzymes.

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