DNA Replication

Preparation and Prerequisites for Replication

Replication occurs during the S ( synthesis Synthesis Polymerase Chain Reaction (PCR)) phase of the cell cycle Cell cycle The phases of the cell cycle include interphase (G1, S, and G2) and mitosis (prophase, metaphase, anaphase, and telophase). The cell’s progression through these phases is punctuated by checkpoints regulated by cyclins, cyclin-dependent kinases, tumor suppressors, and their antagonists. Cell Cycle.
The duration of these cell cycle Cell cycle The phases of the cell cycle include interphase (G1, S, and G2) and mitosis (prophase, metaphase, anaphase, and telophase). The cell’s progression through these phases is punctuated by checkpoints regulated by cyclins, cyclin-dependent kinases, tumor suppressors, and their antagonists. Cell Cycle phases varies considerably in different kinds of cells. For a typical rapidly proliferating human cell with a total cycle time of 24 hours, the G1 (growth) phase might last about 11 hours, S phase S Phase Phase of the cell cycle following g1 and preceding g2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome. Cell Cycle about 8 hours, G2 (growth and preparation for mitosis Mitosis A type of cell nucleus division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. Cell Cycle) about 4 hours, and M ( mitosis Mitosis A type of cell nucleus division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. Cell Cycle) about 1 hour.
The DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure of a human cell mostly exists as 46 chromosomes Chromosomes In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. DNA Types and Structure (23 pairs = 2n) within the nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles. A small fraction of the total is present as mitochondrial DNA Mitochondrial DNA Double-stranded DNA of mitochondria. In eukaryotes, the mitochondrial genome is circular and codes for ribosomal rnas, transfer rnas, and about 10 proteins. DNA Types and Structure, which has approximately 16,500 base pairs containing 37 genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure, all of which are essential for normal mitochondrial function.

Cell cycle, consisting of g1, s, g2, and m phases — Cell cycle, consisting of G1, S, G2, and M phases
Image by Lecturio.

Initiation

Origins of replication: Certain proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis recognize sections of DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure (AT-rich) from which replication can begin.
- Prokaryotes possess only a single origin of replication.
- Eukaryotes have multiple origins of replication. In human DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure, there are more than 30,000 origins of replication, without which the S phase S Phase Phase of the cell cycle following g1 and preceding g2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome. Cell Cycle would last about 40 times longer.
In prokaryotes, a protein called DnaA binds to an origin of replication. In eukaryotes, this is performed by the origin recognition complex (ORC), a 6-unit DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure binding complex.
ATP-dependent helicase DnaB (prokaryotes) unravels the DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure double helix → separates the 2 strands to expose 2 single strands
Helicase (in eukaryotes):
- Moves in the 5′ → 3′ direction along the DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure molecule
- Forms the replication fork by using energy from ATP hydrolysis Hydrolysis The process of cleaving a chemical compound by the addition of a molecule of water. Proteins and Peptides to break the hydrogen bonds between annealed nucleotide bases Bases Usually a hydroxide of lithium, sodium, potassium, rubidium or cesium, but also the carbonates of these metals, ammonia, and the amines. Acid-Base Balance of the complementary strands, thereby separating them
- Bloom’s syndrome is a cancer predisposition disorder caused by mutations in the BLM helicase gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics, 1 of the nearly 100 helicases present in humans.
Single-stranded binding proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis (SSB) bind BIND Hyperbilirubinemia of the Newborn to the unraveled single strands → prevent them from reattaching to each other after they have been separated by helicase
As the 2 strands of template DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure unwind (unravel):
- DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure ahead of the replication fork is forced to rotate in the opposite direction
- DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure becomes twisted around itself without the presence of topoisomerases:
  - Catalyze the reversible breakage and joining of DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure strands
  - Transient breaks produced by these enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes allow the 2 strands of DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure to rotate freely around each other → replication can proceed without causing undue torsional stress on the DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure template, which could lead to breakage of the nucleic acid strands.
  - In prokaryotes, fluoroquinolone antibiotics inhibit topoisomerases II ( DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure gyrase) and IV.
  - In eukaryotes, the chemotherapeutic agents irinotecan Irinotecan A semisynthetic camptothecin derivative that inhibits DNA topoisomerase I to prevent nucleic acid synthesis during s phase. It is used as an antineoplastic agent for the treatment of colorectal neoplasms and pancreatic neoplasms. Microtubule and Topoisomerase Inhibitors and topotecan Topotecan An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA topoisomerases, type I. Microtubule and Topoisomerase Inhibitors inhibit topoisomerase I, whereas etoposide Etoposide A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the g2 and s phases of the cell cycle. Microtubule and Topoisomerase Inhibitors and teniposide Teniposide A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Teniposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent cells from entering into the mitotic phase of the cell cycle, and lead to cell death. Teniposide acts primarily in the g2 and s phases of the cycle. Microtubule and Topoisomerase Inhibitors inhibit topoisomerase II Topoisomerase II DNA topoisomerases that catalyze ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. These enzymes bring about relaxation of the supercoiled DNA and resolution of a knotted circular DNA duplex. Fluoroquinolones.

Dna replication — DNA replication or DNA synthesis is the process of copying a double-stranded DNA molecule. This process is paramount to all life as we know it.
Image: “DNA Replication” by Mariana Ruiz. License: Public Domain

Polymerase	Function	Exonuclease activity
α	Synthesizes the RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure primer and initiates DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure synthesis Synthesis Polymerase Chain Reaction (PCR) along the lagging strand	3′ → 5′
β	Repairs DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure	None
γ	Replicates mitochondrial DNA Mitochondrial DNA Double-stranded DNA of mitochondria. In eukaryotes, the mitochondrial genome is circular and codes for ribosomal rnas, transfer rnas, and about 10 proteins. DNA Types and Structure	3′ → 5′
δ	Synthesizes the lagging strand, filling DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure gaps after removal of primer	3′ → 5′
ε	Synthesizes the leading strand	3′ → 5′ and 5′ → 3′

Elongation

A primer is necessary for the synthesis Synthesis Polymerase Chain Reaction (PCR) of daughter strands of DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure
- It is a short piece of RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure (8–10 base pairs).
- Complementary to template strand
- Synthesized by primase (a DNA-dependent RNA polymerase DNA-dependent RNA polymerase Enzymes that catalyze DNA template-directed extension of the 3′-end of an RNA strand one nucleotide at a time. They can initiate a chain de novo. In eukaryotes, three forms of the enzyme have been distinguished on the basis of sensitivity to alpha-amanitin, and the type of RNA synthesized. Virology)
  - In eukaryotes, it is a subunit of DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure polymerase alpha.
DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure synthesis Synthesis Polymerase Chain Reaction (PCR)
- Replication occurs continuously on the leading strand and discontinuously on the lagging strand.
Leading strand
- Replication continuous due to free 3′ OH group
- Requires only 1 primer
Lagging strand
- Replication discontinuous to ensure always a free 3′ OH group for elongation Elongation Polymerase Chain Reaction (PCR)
- Forms Okazaki fragments (1,000–2,000 nucleotides Nucleotides The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. Nucleic Acids in length)
- A primer is needed for each segment of DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure.
Proceed in 5′ → 3′ direction
Base pairs are added to the free 3′ OH end of the daughter strand.
Catalyzed by DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure polymerase (polymerase δ in eukaryotes and DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure polymerase III in prokaryotes)
- Forms ester bond between 3′ OH group to α-phosphate of nucleotide
- Pyrophosphate released
Proofreading
- Accomplished only by polymerases with 3′ → 5′ exonuclease activity
Primer removal
- Excised in the opposite direction of synthesis Synthesis Polymerase Chain Reaction (PCR) (i.e., 5′ → 3′)
- Prokaryotes: by RNase H and the 5′ → 3′ exonuclease activity of DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure polymerase I
- Eukaryotes: by FEN-1 (flap endonuclease-1)
Filling the gaps
- Gaps filled with complementary deoxynucleotides
- Prokaryotes: DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure polymerase I adds deoxynucleotides one at a time then proofreads.
- Eukaryotes: DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure polymerase δ
Joining the ends
- DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure ligase joins the free ends of the daughter strands.
- Reaction involves:
  - Transfer of AMP to 5′ phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes end
  - AMP is cleaved and 5′ phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes end bound to 3′ OH end of other fragment.
After the duplication of the DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure, there are 46 double chromatid chromosomes Chromosomes In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. DNA Types and Structure (4n)
- Following anaphase Anaphase The phase of cell nucleus division following metaphase, in which the chromatids separate and migrate to opposite poles of the spindle. Cell Cycle and cytokinesis Cytokinesis The process by which the cytoplasm of a cell is divided. Meiosis (of mitosis Mitosis A type of cell nucleus division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. Cell Cycle) reduced to 46 single chromatid chromosomes Chromosomes In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. DNA Types and Structure (2n)

Termination

Initiated by binding of termination proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis (ter proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis) to termination sequences
Different termination in prokaryotes (circular DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure) and eukaryotes (linear DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure)
Eukaryotic Eukaryotic Eukaryotes can be single-celled or multicellular organisms and include plants, animals, fungi, and protozoa. Eukaryotic cells contain a well-organized nucleus contained by a membrane, along with other membrane-bound organelles. Cell Types: Eukaryotic versus Prokaryotic chromosomes Chromosomes In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. DNA Types and Structure → linear
- A gap will exist.
If during replication the complementary primer is at the 5′-OH end of the daughter strand, there is no free 3′-OH end for ligation Ligation Application of a ligature to tie a vessel or strangulate a part. Esophageal Atresia and Tracheoesophageal Fistula.
The gap left by the primer cannot be filled; this means that after each replication, a small piece at the end of the DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure is missing.
This is the reason for a non-coding repetitive sequence (GGGTTA) with over 10,000 base pairs at the end of the eukaryotic Eukaryotic Eukaryotes can be single-celled or multicellular organisms and include plants, animals, fungi, and protozoa. Eukaryotic cells contain a well-organized nucleus contained by a membrane, along with other membrane-bound organelles. Cell Types: Eukaryotic versus Prokaryotic chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics (telomere).
Coding sequences ( genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure) only stop being completely replicated after 30–50 cell cycles; this limits the life expectancy Life expectancy Based on known statistical data, the number of years which any person of a given age may reasonably expected to live. Population Pyramids of most somatic cells.

Telomeres and Clinical Relevance

Telomeres
- Non-coding DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure fragments at 3′ ends of chromosomes Chromosomes In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. DNA Types and Structure
- Each telomere consists of several thousand base pairs (tandem repeats of TTAGGG)
- Function of a telomere:
  - Prevents the loss of structural genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure
  - The lagging strand becomes shorter after each round of replication due to the removal of the RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure prime so DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure is lost from the telomere rather than from the coding sequence.
  - Functions like a cellular clock since the cell undergoes replicative senescence or apoptotic cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death when the telomere length goes below a critical limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation. The length of telomeric DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure determines the lifespan of a cell in culture.
Telomerase
- Special reverse transcriptase Reverse transcriptase A reverse transcriptase encoded by the pol gene of HIV. It is a heterodimer of 66 kda and 51 kda subunits that are derived from a common precursor protein. The heterodimer also includes an RNAse h activity that plays an essential role the viral replication process. HIV Infection and AIDS that carries its own RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure template
- Maintains telomeres
- Present in rapidly dividing cells, embryonic and cancer cells
  - Activity is especially enhanced in cancer cells so their telomeres stay long and they can keep dividing without regard to a molecular clock even if they reach the end of their normal lifespan.

References

Alberts, B., Johnson, A., Lewis, J., Morgan, D., Raff, M., Roberts, K., & Walter, P. (2022). Molecular biology of the cell (7th ed.). W. W. Norton & Company.
Cooper, G. M. (2019). The cell: A molecular approach (8th ed.). Sinauer Associates.
Lodish, H., Berk, A., Kaiser, C. A., Krieger, M., Bretscher, A., Ploegh, H., Amon, A., & Martin, K. C. (2021). Molecular cell biology (9th ed.). W. H. Freeman.
Nussbaum, R. L., McInnes, R. R., & Willard, H. F. (2023). Thompson & Thompson genetics in medicine (9th ed.). Elsevier.
Oestreich, K. J., & Weinmann, A. S. (2024). Advances in understanding telomere maintenance and its implications for cellular aging and cancer. Nature Reviews Molecular Cell Biology, 25(3), 156-170.
Pollard, T. D., Earnshaw, W. C., Lippincott-Schwartz, J., & Johnson, G. T. (2020). Cell biology (3rd ed.). Elsevier.
Reece, J. B., Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V., & Orr, R. B. (2023). Campbell biology (13th ed.). Pearson.

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Preparation and Prerequisites for Replication

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