BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012

Chapter 10. NUCLEIC ACID METABOLISM

10.6.DNA Biosynthesis (Replication)

General Principles. All Cells undergo division throughout their life span. Some cells divide continuously (such as stem cells), others only a finite number of times until Cell death (apoptosis) occurs, and some divide merely a few times before undergoing differentiation. During Cell Division, all cellular components are duplicated, thereby ensuring that daughter cells can function fully in the future.

A particularly crucial process during cell division is the duplication of genomic DNA. The uniqueness of this phenomenon lies in the fact that DNA itself encodes the information for The Mechanism of its own duplication: some genes encode Enzymes that synthesize nucleotide precursors for DNA, others encode Proteins that assemble activated NUCLEOTIDES into polynucleotide chains; there are genes that coordinate DNA Synthesis with other cellular events, as well as genes encoding proteins that pack (compact) DNA into Chromatin.

Furthermore, during synthesis, DNA acts as a template and determines the precise order in which nucleotides are incorporated into new strands. This template allows Genetic information to be reproduced with high fidelity and efficiency. Accurate copying of the DNA template is ensured by THE PRINCIPLE OF complementarity of nucleotide nitrogenous bases, whereby adenine pairs with thymine, and guanine with cytosine. However, despite providing high reliability, the complementarity principle is not error-free. Random deviations (fluctuations) occur in The Structure of the incoming nucleotides and those within the template strand, which can lead to mispairing and the incorporation of incorrect nucleotides. For instance, an adenine nucleotide may temporarily assume an imino form, or thymine an enol form. Under such conditions, chain elongation typically stalls. Polymerase enzymes possess an efficient proofreading system—they excise the misincorporated, unpaired nucleotide almost immediately after its addition to the growing chain terminus, and synthesis resumes.

The complementary pairing of purine and pyrimidine nucleotides in the two polynucleotide strands of the DNA double helix proceeds in a semiconservative manner. This means that upon completion of the process, the original DNA molecules are half-renewed. In each daughter molecule, one strand is parental, and the other is newly synthesized. Moreover, unlike RNA Synthesis, METABOLISM/36.html">DNA Replication is a symmetrical process, as both strands of the parental DNA serve as templates.

In the small genomes of eukaryotes and prokaryotes, DNA replication initiates at a specific locus called the origin and proceeds quite rapidly: in E. coli, The rate of DNA synthesis is 1,700 Base Pairs per second, allowing the entire genome (4.7·10⁶ base pairs) to be copied in 40 minutes. In larger cells, such as animal cells, DNA replication is slower, proceeding at a rate of approximately 50 base pairs per second. However, initiation in this case occurs simultaneously at multiple sites along the DNA molecule; that is, eukaryotic DNA generates numerous replication units known as replicons. As a result, the Drosophila chromosome, for example, which consists of 6.5·10⁷ base pairs, is replicated within just a few minutes.

DNA Biosynthesis is a sequential process regulated primarily at the initiation stage. Once commenced, replication continues until the entire replicon has been duplicated. The frequency of initiation is governed by the interaction of regulatory protein(s) with THE ORIGIN OF replication. Unlike RNA synthesis, replicative DNA synthesis occurs strictly during the S phase of the mitotic Cell Cycle AND only once per cell cycle. Special proteins known as cyclins (types A, B, D, and E) participate in this Cell cycle regulation.