4 Fundamental Molecular Genetics Mechanisms

Overview of Molecular Genetics

• Focus on mechanisms of DNA structure & function, chromosome structure and regulation, homologous recombination, mobile genetic elements, and viruses.

Chromosomes in Eukaryotes

• Chromosomes become visible as cells prepare to divide; in non-dividing cells, DNA exists as chromatin.

• Chromatin is less condensed, allowing for extended conformation and DNA access.

Structure of DNA

• DNA comprises two antiparallel complementary strands of nucleotides.

  • Nitrogen bases: Purines (adenine and guanine) & Pyrimidines (cytosine and thymine).

  • Base + pentose (ribose or deoxyribose) = nucleoside.

  • Nucleoside + phosphate = nucleotide.

  • A pairs with T (2 H-bonds), C pairs with G (3 H-bonds).

DNA Complementarity and Structure

• Bases form hydrogen bonds:

  • A-T (2 bonds) and C-G (3 bonds).

  • DNA strands are oriented in 5' to 3' direction.

DNA Function

• The double helix structure enables hereditary information transfer.

• Eukaryotic DNA is organized into linear chromosomes maintaining gene order and distance.

Chromosome Structure

• Each chromosome has a centromere and telomeres at the ends.

• Chromosomes are stained for visual representation and numbered by size.

Chromosome Number

• Normal human chromosome count: 46 (44 somatic + 2 sex chromosomes: XX or XY).

• Related species may exhibit significant differences in chromosome numbers.

Chromosome States During Cell Cycle

• Interphase is the most active phase; DNA exists in extended form for transcription and replication.

• Chromosome packaging occurs in multiple levels, leading to significant condensation for mitosis.

DNA and Chromatin Organization

• Chromatin is a complex of DNA and histones, forming nucleosomes (basic units).

  • Nucleosomes consist of 145 base pairs around histone octamers (H2A, H2B, H3, H4).

• Chromatin exists in two forms: euchromatin (active, decondensed) and heterochromatin (inactive, condensed).

Regulation of Chromatin Structure

• Chromatin-remodeling complexes modify the accessibility of DNA by loosening nucleosomal structures.

• Interphase chromosomes organize within the nuclear envelope, affecting gene expression.

• Examples: X chromosome inactivation as a bar body, impacting dosage compensation in females.

DNA Replication

• Hereditary information is passed via semi-conservative replication, where each strand serves as a template.

• DNA replication occurs in a 5' to 3' direction, requiring RNA primers synthesized by primase.

Initiation of Replication

• Origins of replication: sites where replication begins, enriched in A-T pairs.

• In eukaryotes, multiple origins are necessary for efficient replication.

Mechanisms of DNA Replication

• Replication forks are the sites of active DNA synthesis with leading and lagging strands.

• Okazaki fragments form on the lagging strand and are joined by ligases.

• DNA polymerases ensure replication fidelity through base pairing and proofreading mechanisms.

DNA Damage and Repair Mechanisms

• DNA can suffer mutations or damage from replication errors or external factors.

• Key repair mechanisms include base-excision repair (BER), nucleotide-excision repair (NER), and mismatch repair (MMR).

• Homologous recombination repairs double-strand breaks and ensures fidelity in genetic information.

Transposable Elements and Viruses

• Transposable elements can move within the genome and affect genetic variation; examples include L1 and Alu in humans.

• Viruses exploit host cell machinery for replication and propagation, exemplified by retroviruses that reverse transcribe RNA into DNA.

• Both mobile genetic elements and viruses possess components necessary for their movement or replication, contributing to genetic diversity.