MEDICAL BIOLOGY, HUMAN ANATOMY, PHYSIOLOGY AND PATHOLOGY - Ya.I.Fedonyuk 2010

BIOLOGY

SECTION 1. BIOLOGICAL FOUNDATIONS OF HUMAN VITAL ACTIVITY

1.3. MOLECULAR-GENETIC AND CELLULAR LEVELS OF LIFE ORGANIZATION

1.3.3. Hereditary apparatus of eukaryotic cells and its functioning - molecular level

METABOLISM/36.html">DNA Replication

Replication (syn.: self-duplication, self-reproduction, autoreplication of DNA molecules) is the synthesis of DNA on a DNA template, which occurs during the S-phase of interphase and ensures the accurate copying of Genetic information. The ability to self-duplicate is a unique property of DNA, inherent only to DNA and absent in any other chemical substance. The replication scheme was initially proposed by J. Watson and F. Crick (Fig. 1.40). According to this scheme, The Double Helix of the parent DNA molecule separates into two strands, each of which serves as a template for synthesizing a new strand based on THE PRINCIPLE OF complementarity. As a result, one parent DNA molecule produces two daughter molecules that are exact copies of the parent. Since each newly formed daughter molecule contains one old (parental) strand and one new strand, this replication mechanism is called semiconservative. The process is ensured by the coordinated action of A number of Enzymes. DNA Synthesis is catalyzed by the enzyme DNA polymerase. There are several types of DNA polymerases. The DNA polymerase enzyme was first isolated in 1957 from the bacterium Escherichia coli by A. Kornberg. It was found that DNA polymerase is incapable of initiating de novo DNA strand synthesis; therefore, its activity requires the presence of pre-existing DNA in the system (the so-called DNA primer), i.e., a DNA strand with a free 3'-OH end. DNA polymerase ensures the attachment of deoxynucleotides to the 3'-OH end of the DNA primer. The presence of a DNA template in this system determines which specific NUCLEOTIDES must attach to the DNA primer. In the presence of a DNA primer and a DNA template, DNA polymerase ensures the synthesis of a daughter DNA strand complementary to one of the parent DNA strands. In the in vivo system, The Role of the DNA primer is performed by An RNA primer.

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Fig. 1.40. DNA replication According to the scheme of J. Watson and F. Crick: 1, 2 - parent DNA strands; 1a, 2a - daughter DNA strands.

Replication begins at the ori site (from English origin), where the unwinding of the DNA double helix occurs, along with the local Separation of its strands, stabilization of single-stranded DNA, The Emergence of a Y-shaped Structure (Replication fork) from the two separated strands, and the Synthesis of the RNA primer. The synthesis of new strands proceeds exclusively in the 5' → 3' direction. The initiation of synthesis is preceded by The formation of RNA primers, to the 3'-OH end of which the enzyme DNA polymerase attaches deoxynucleoside monophosphates, forming the new strand. The synthesis of RNA primers is catalyzed by the enzyme RNA polymerase, or primase. Since DNA strands are antiparallel (5' → 3' and 3' → 5') and DNA polymerase attaches free nucleotides only to the 3'-OH end, the synthesis of the two daughter strands proceeds via different mechanisms. One strand (the leading strand) is synthesized continuously from the RNA primer in the direction of movement of the replication fork, whereas the second strand (the lagging strand) is synthesized discontinuously, producing short fragments known as Okazaki fragments (R. Okazaki was the Japanese scientist who first discovered them), in the direction opposite to the movement of the replication fork (Fig. 1.41). Each fragment begins with a corresponding RNA primer. These short stretches of the newly synthesized polynucleotide strand are subsequently joined together into a single strand by the enzyme DNA ligase. Upon completion of replication, the RNA primers are removed, and nucleotides complementary to the DNA template are incorporated into these gaps.

Fig. 1.41. DNA replication according to the scheme of R. Okazaki.

A region of DNA controlled by a single ori site is called a unit of replication (replicon). Prokaryotic DNA has a single ori site, and the entire molecule duplicates as a single replicon. Eukaryotic DNA contains many ori sites and, accordingly, many replicons, which is a prerequisite for ensuring that giant eukaryotic DNA molecules can complete duplication within the duration of a single Cell Cycle.