DNA Replication

Big Idea: DNA is located in the nucleus of a cell and codes for all information the body needs to develop.

Key Concepts:
- Genetic material is defined as material that codes for traits in an organism. - DNA Repair: There are mechanisms in place to repair damaged DNA to maintain the integrity of genetic information.

Nucleotides: Building blocks of DNA.   - Composed of:
    - A 5-carbon sugar (deoxyribose)
    - A phosphate group (attached at the 5' carbon of the sugar)
    - A nitrogenous base (Adenine, Thymine, Cytosine, Guanine)
  - Each nucleotide is linked to the next via phosphodiester bonds, forming a sugar-phosphate backbone.

Polarity: Each DNA strand has directional polarity (5' to 3' and 3' to 5').
Phosphodiester Bond: Bond between adjacent nucleotides - Formed between phosphate group of one nucleotide and the 3' OH group of another nucleotide.

Semiconservative Replication: Each daughter DNA molecule consists of one parental strand and one newly synthesized strand.
Requirements for DNA Replication:
  - A template DNA strand (the parental DNA)
  - Enzymes to facilitate the process (e.g., DNA polymerase)
  - Building blocks (nucleotide triphosphates) to synthesize new strands.

Initiation: Opening of the DNA helix to allow replication.
Elongation: New DNA strands are synthesized by DNA polymerase.
Termination: The cessation of replication once the entire molecule is copied.

DNA Polymerase:
- Enzymes that synthesize new DNA strands by adding complementary nucleotides to the existing strand. - Must add new nucleotides to the 3' end of an existing strand, synthesizing in a 5' to 3' direction.
Primase: Synthesizes RNA primers for replication.
Ligase: Joins Okazaki fragments on the lagging strand.

Utilizes E. coli as a model organism for understanding replication processes.
Origin of replication: Uniquely identified as the point at which DNA replication begins (oriC).
Three types of E. coli DNA Polymerases:
1. DNA Polymerase I (Pol I): Removes RNA primers and replaces them with DNA. 2. DNA Polymerase II (Pol II): Involved in DNA repair.
3. DNA Polymerase III (Pol III): Main enzyme for replication, has proofreading capabilities (3' to 5' exonuclease).

Synthesized discontinuously due to the antiparallel nature of DNA, resulting in Okazaki fragments.
Each Okazaki fragment requires a new RNA primer for synthesis before eventually being connected by ligase.

More complex than prokaryotic replication due to: - Multiple chromosomes
- Larger quantities of DNA.
Utilizes multiple origins of replication on linear chromosomes.
Key enzymes include: - DNA polymerase α: Primase with polymerase activity. - DNA polymerase ε: Synthesizes the leading strand. - DNA polymerase δ: Synthesizes the lagging strand.

Telomeres: Structures at chromosome ends that protect from degradation; consist of repeating DNA sequences.
Telomerase: An enzyme that extends telomeres using an RNA template, countering the issue of repeated shortening during replication.

Constantly necessary due to spontaneous mutations, errors, and damage from external factors (mutagens).
DNA polymerases have proofreading abilities to fix errors that arise during replication.
Two Categories of DNA Repair:
1. Specific Repair: Targets specific types of DNA damage. 2. Nonspecific Repair: Employs a uniform mechanism to repair various forms of DNA damage.

Mismatch Repair (MMR): Corrects base-pair mismatches.
Photorepair: Repairs UV-induced thymine dimers using the photolyase enzyme.
Excision Repair: Damaged area is recognized and removed, followed by DNA synthesis using the complementary strand as a template.

Understanding DNA structure, replication, and repair mechanisms is crucial for genetics and cellular biology, impacting areas such as cancer research and treatment, developmental biology, and evolutionary studies.