BIOCHEMISTRY - Key Regulators and Biological Fluids of the Human Body - 2016

3. NUCLEIC ACIDS

3.4. DNA Replication

Before Cell Division, DNA is duplicated. This process is called Replication.

Stages of replication:

- unwinding of the helix;

- breaking of Hydrogen Bonds;

- Synthesis of the second strands;

- ligation of the parental and daughter strands.

3.4.1. Mechanism of Replication

Specific Enzymes called helicases unwind the elongated strands of particular DNA regions by breaking hydrogen bonds. A specialized protein specifically binds to one of the DNA strands, preventing its re-association into a double helix. This protein is known as the SSB (single-stranded binding) protein.

The enzyme DNA polymerase moves along the separated strands and builds new nucleic acid chains.

Termination of replication is mediated by terminators—specific nucleotide sequences that, when reached by DNA polymerase, halt the synthesis of the new DNA strand.

3.4.2. Principles of Replication

Complementarity. Each strand of the parental DNA serves as a template for the synthesis of a new complementary strand. The second strand is synthesized on the first According to the base-pairing rules: A - T, G - C.

Semiconservative nature. Each daughter cell receives only one intact (conserved) strand of the parental DNA.

Antiparallelism. Each DNA strand has a specific orientation: one end carries a hydroxyl group (-OH) at the 3' carbon of the sugar, while the other end carries a phosphate group at the 5' carbon of the sugar. DNA polymerase operates in only one direction—from the 3' end to the 5' end. Consequently, the synthesis of new strands proceeds in opposite directions, i.e., in an antiparallel manner.

Discontinuity. For replication to initiate, the parental strands must be: 1) straightened and 2) unwound. Under cellular conditions, this is impossible to achieve all at once, so replication initiates simultaneously at multiple sites.

The segment of DNA between two replication initiation sites is called a replicon, which serves as the unit of replication.

Replication forks are the sites where daughter strands are synthesized (approximately 1,000 NUCLEOTIDES in length), which move along the DNA molecule.

Thus, DNA Synthesis occurs in fragments (discontinuously).

To correct replication errors that inevitably occur during DNA synthesis, a specialized enzyme system known as DNA Repair exists to fix abnormalities in The nucleotide sequence.

If replication errors are not removed by the DNA repair system, or if nucleotide sequence alterations occur prior to replication, Mutations arise, which inevitably leads to the distortion of Genetic information (the program).

Mutations can be spontaneous (occurring without an apparent cause) or induced (resulting from exposure to Mutagenic Factors).

Broadly classified, mutations are subdivided into point (Gene) mutations, chromosomal mutations (detectable at the level of individual Chromosomes), and genomic mutations (abnormalities in chromosome number).