![]() ![]() This strand is called the leading strand. As the strands are antiparallel with opposing polarity and since DNA polymerases can only synthesize DNA in the 5′ to 3′ direction, only one strand is continuously synthesized. Each strand serves as a template for the DNA polymerase to catalyze the addition of the correct base during synthesis of a new complementary strand. The complementary base pairing between the nitrogen bases A-T and G-C underlies the semi-conservative nature of DNA replication, which results in a duplicated genome with one parental strand and one newly synthesized strand. The mechanism of DNA replication is greatly influenced by DNA structure. ![]() The precise mechanisms of origin licensing and origin firing in two separate phases of the cell-cycle ensure that DNA replication occurs only once per cell-cycle. Once origins fire, DNA synthesis begins and the initiator proteins are degraded or exported out of the nucleus to prevent re-replication. The helicase is inactive in the pre-RC and is activated only in the S phase when origins ‘fire’ due to the activity of CDK/ DDK kinases. This assembly of the pre-replicative complex (pre-RC) at origins during G1 phase is called ‘origin licensing’ FIG. The eukaryotic replicative helicase is a complex of proteins called the CMG helicase consisting of Cdc45, Mcm2-7 and GINS proteins. In eukaryotes, initiator proteins ORC, Cdc6 and Cdt1 recruit the replicative helicase. Replication commences at a single origin in prokaryotes and at multiple origins in eukaryotes, however, the basic mechanism of replication is conserved in all organisms. DNA replication is initiated at specific sites in the genome known as the ‘origins’ which are recognized and bound by origin binding proteins. The stage for DNA replication is set in the G1 phase of the cell cycle and DNA is synthesized in the S phase. Defects in DNA replication could give rise to damaging mutations including those that cause cancer. These checkpoints ensure that replication of DNA occurs just once per cell cycle. A number of proteins participate in DNA replication and the process is subject to scrutiny by cell surveillance mechanisms called cell cycle checkpoints. DNA replicates in the S phase of the cell cycle and initiates at specific regions in the DNA sequence known as DNA replication ‘origins’. DNA replication is an essential process and the basic mechanism is conserved in all organisms. This ensures that each daughter cell gets a copy of the genome, and therefore, successful inheritance of genetic traits. Cells must replicate their DNA before they can divide. ![]()
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