Molecular Basis of Inheritance

Definition of DNA: DNA, or deoxyribonucleic acid, is a polymer made up of nucleotides.
Components of Nucleotides:
- Nitrogenous base
- Deoxyribose sugar (with the absence of an oxygen atom, hence "deoxy")
- Phosphate group
Formation of a DNA Polymer: Nucleotides are linked together in sequences to form a long polymer, creating DNA strands.

Double Helix: DNA is structured as a double helix comprising two strands.
- The strands have a sugar-phosphate backbone, with alternating sugar and phosphate groups.
- Orientation of Strands: The strands run in opposite directions, referred to as antiparallel.
Ends of DNA Strands:
- 5' End: Contains a phosphate group at the terminal end (5-Carbon).
- 3' End: Contains a hydroxyl group at the terminal end (3-Carbon).
Base Pairing:
- The nitrogenous bases form pairs in the middle of the double helix:
- Adenine (A) pairs with Thymine (T) via 2 hydrogen bonds.
- Cytosine (C) pairs with Guanine (G) via 3 hydrogen bonds.
- Importance of pairing purines with pyrimidines for structural integrity of DNA.

Model of DNA Replication: DNA is replicated via a semi-conservative model.
- Mieses and Stahl Experiment: Demonstrated the semi-conservative model using isotopes of nitrogen in bacterial DNA.
- Alternatives considered:
- Conservative: Both original strands remain together, and new strands form entirely.
- Dispersive: New and old segments interspersed.
- Conclusion: DNA replication yields one old strand and one new strand per double helix.

Origins of Replication:
- Prokaryotes: Typically have one origin of replication.
- Eukaryotes: May have hundreds to thousands, facilitating rapid replication.
Formation of Replication Bubble: As replication begins, strands are unwound and separated, leading to a replicated area or bubble.
Enzymes Involved:
- Helicase: Unwinds and separates the DNA strands at the replication fork.
- DNA Polymerase: Catalyzes the synthesis of new DNA strands by adding nucleotides.
- Primase: Synthesizes a short RNA primer to provide a starting point for DNA polymerase.

DNA strands are synthesized in a 5' to 3' direction.
- New nucleotides are added to the 3' end of the growing strand.
Leading Strand:
- Synthesized continuously toward the replication fork.
Lagging Strand:
- Synthesized in short segments called Okazaki fragments, due to opposing direction.
- Requires multiple primers and involves discontinuous synthesis.
DNA Ligase: Joins Okazaki fragments together to create a continuous strand.

Unwinding:
- Helicase unwinds double helix structure.
Synthesis:
- DNA polymerase synthesizes new strands from the template strand.
Proofreading: DNA polymerase checks and replaces incorrect nucleotides.

Mutations: Changes in DNA sequences due to errors or uncorrected nucleotides during replication can lead to mutations.
Enzymes for Correction:
- Certain enzymes exist to correct base pairing errors beyond the capacity of DNA polymerase.
Mutation Transmission: Mutations in germline cells can be passed to future generations, creating genetic diversity.

Eukaryotic chromosomes experience problems with replication at the 5' ends due to the limitations of DNA polymerase.
Result: Shortened chromosomes upon replication cycles, leading to shorter DNA molecules and potential gene loss.
Solution: Telomeres are protective nucleotide sequences at chromosome ends.
- Telomerase: An enzyme that extends telomeres in germline cells to maintain chromosome length.
Implications for Aging and Cancer:
- Shortened telomeres are implicated in aging processes and cancer cell proliferation due to active telomerase.

Understanding DNA structure and replication is essential for genetics, heredity, and molecular biology.
Understanding enzymes involved is vital for comprehending cellular replication and the implications of mutations on inheritance.