The 2’,3’-dideoxynucleosides can be used as reagents to inhibit DNA replication.
ID: 67019 • Letter: T
Question
The 2’,3’-dideoxynucleosides can be used as reagents to inhibit DNA replication. These analogs must be converted to dideoxynucleoside triphosphates in order to have a measurable effect on DNA synthesis. When incorporated into a growing DNA chain, a single dideoxyribonucleoside residue can effectively block subsequent chain extension.
a) Why must a 2’,3’-dideoxyribonucleoside be converted to a dideoxyribonucleoside triphosphate to be incorporated into DNA?
b) What feature of 2’,3’-dideoxyribonucleoside is most likely to account for inhibition of DNA chain extension?
FIGURE 4.4 HOCH2B 0.Explanation / Answer
a) 2’,3’-dideoxyribonucleoside must be converted to a dideoxyribonucleoside triphosphate to be incorporated into DNA because during the DNA synthesis the elongation of chain takes place by forming phosphodiester linkages. And with out convert 2’,3’-dideoxyribonucleoside must be converted to a dideoxyribonucleoside triphosphate (i.e. nucleoside to nucleotide) it cannot be incorporate in DNA chain. Thus the phosphate groups must me added (or it must be converted into dideoxyribonucleoside triphosphate).
b) DNA polymerase has 5'-3' activity. All known DNA replication systems require a free 3' hydroxyl group for synthesis. 2‘,3‘-Dideoxynucleoside triphosphates inhibit the chain elongation of a given primer catalyzed by the DNA polymerase because it lacks -OH group at 3' carbon due to which the further attack of next necleotide is not possible on it and hence, the phosphodiester bond is not formed terminating the DNA chain extension.
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