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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.