DNA synthesis initiation

DNA replication proceeds by the synthesis of one new strand on each of the parental strands. This mode of replication is called semiconservative, and it appears to be universal. DNA synthesis initiates from a primer at a unique point on a prokaryotic template such as the E. coli chromosome. From the initiation point, DNA synthesis proceeds bidirectionally on the circular bacterial chromosome. The bidirectional mode of synthesis is not followed by all chromosomes. For some chromosomes, usually small in size, replication is unidirectional. 

Grooke, E. (1995) DNA synthesis initiated at oriG in vitro replication reactions, in Methods in Enzymology, Vol. 262 (ed. J.L. Gampbell), Academic Press, New York, pp. 500-506. 

Antibiotic A201A. Antibiotic A201A (23), produced by S. capreolus is an /V -dimethyladenine nucleoside stmcturaHy similar to puromycin (19). Compound (23) which contains an aromatic acid and monosaccharide residues (1,4), inhibits the incorporation of amino acids into proteins but has no effect on RNA or DNA synthesis. Compound (23) does not accept polypeptides as does (19), and does appear to block formation of the initiation complex of the SOS subunit. It may block formation of a puromycin-reactive ribosome. 

DNA synthesis during S phase of the cell cycle resulting in a doubling of the genomic DNA. Replication can be subdivided into three distinct phases initiation, elongation, and termination. 

Figure 36-14. The initiation of DNA synthesis upon a primer of RNA and the subsequent attachment of the second deoxyribonucleoside triphosphate.

Othet cyclins and CDKs are involved in different aspects of cell cycle progression (Table 36-7). Cychn E and CDK2 form a complex in late Gl. Cychn E is tapidly degraded, and the released CDK2 then fotms a complex with cyclin A. This sequence is necessaty fot the initiation of DNA synthesis in S phase. A complex between cychn B and CDKl is tate-hmiting fot the G2/M transition in eukatyotic cells. 

Klaunig et al. (1991) found that hepatocyte DNA synthesis increased significantly in male mice exposed to trichloroethylene by gavage for up to 14 days, but no such increase was seen in female mice or in renal DNA synthesis in either sex. Similar exposures in rats produced increases in renal DNA synthesis in males, but no such increase in females, or in hepatic DNA synthesis in either sex. These results correlate well with observed species- and gender-specific trichloroethylene carcinogenicity, and the study authors suggest that trichloroethylene acts as a tumor promoter to induce proliferation of previously initiated cells. 

All DNA polymerases add mononucleotides to the 3 end of an existing primer. Consequently a special primer is needed for DNA to replicate in its entirety. RNA polymerases can initiate polymer synthesis without a primer thus short RNA primers are used to initiate DNA synthesis. 

A primer is a very special sequence, which plays an important role in duplication, (i) In RNA, it is a short sequence that is paired with one strand of DNA and provides a free 3 -OH terminus at which a DNA polymerase starts synthesis of a deoxyribonucleotide chain, (ii) In DNA, it is another short sequence, which is complementary to a sequence of messenger RNA and allows reverse transcriptase to start copying the adjacent sequences of mRNA. (iii) In retroviruses, it is a cellular transfer RNA whose elongation initiates RNA-directed DNA synthesis by the DNA polymerase. 

The mechanism of action of nalidixic acid against E. coli. was found to be inhibition of DNA synthesis.(25) No selective effect on purines or pyrimidines was found and no inhibition of initiator synthesis was demonstrated. In addition the nalidixic acid could be removed from cultures after exposures up to 75 minutes by rinsings and cells would recover from the block. 

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