T

FIGURE 9-11 Photoreactivation. UV irradiation causes formation of thymine dimers. Upon exposure to light, DMA photolyase breaks the nng formed between the dimers to restore the two thymine residues.

a methyltransferase removes the methyl group from the guanine residue by transferring it to one of its own cysteine residues (Figure 9-12). This is very costly to the cell because the methyllransferase is not catalytic; having once accepted a methyl group, it cannot be used again.

Base Excision Repair Enzymes Remove Damaged Bases by a Base-Flipping Mechanism

The most prevalent way in which DNA is cleansed of damaged bases is by repair systems that remove and replace the altered bases. The two principal repair systems are base excision repair and nucleotide excision repair. In the base excision repair, an enzyme called a glycosylate recognizes and removes the damaged base by hydrolyzing the gtycosidic bond (Figure 9-13). The resulting abasic sugar is removed hum the DNA backbone in a further endonucleolytic step, Endonucleolytic cleavage also removes apurinic and apyiimidinic sugars that arise by spontaneous hydrolysis. After the damaged nucleotide has been entirely removed from the backbone, a repair DNA polymerase and DNA ligase restore an intact strand using the undamaged strand as a template,

DNA glycosylases are lesion-specific and cells have multiple DNA glycosylases with different specificities. Thus, a specific glycosylate recognizes uracil (generated as a consequence of deammation of cyto-sineji and another is responsible for removing oxoG (generated as a consequence of oxidation of guanine). A total of eight different DNA glycosylases have been identified in the nuclei of human cells.

Cleansing the genome of damaged bases is a formidable problem because each base is buried in the DNA helix. How do DNA glycosylases detect damaged bases while scanning the genome? Evidence indicates that these enzymes diffuse laterally along the minor groove of the DNA until a specific kind of lesion is detected. But how is the methyltransferase sh

FIGURE 9-12 Methyl group removal.

Methyl transferase catalyzes the transfer of the methyl group cn Dimethyl guanine to a cysteine residue on the enzyme, thereby restoring the normal C in DMA.

FIGURE 9-12 Methyl group removal.

Methyl transferase catalyzes the transfer of the methyl group cn Dimethyl guanine to a cysteine residue on the enzyme, thereby restoring the normal C in DMA.

methyltransferase sh normal base

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