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DNA Replication and the Central Dogma

The Central Dogma of Molecular Biology#

The central dogma of molecular biology, first proposed by Francis Crick in 1958, describes the flow of genetic information within a biological system. It states that DNA is transcribed into RNA, which is then translated into protein.

DNA → RNA → Protein

This fundamental principle underpins all life processes and is essential for understanding genetics, cell function, and heredity.

DNA Structure - A Quick Recap#

Before diving into replication, let’s recall why DNA’s structure is so remarkable:

TIP

The double helix structure of DNA, discovered by Watson and Crick in 1953, is perfectly suited for its function of storing and copying genetic information.

Key features include:

  • Double-stranded helix - Two strands wound around each other
  • Complementary base pairing - A pairs with T (2 hydrogen bonds), C pairs with G (3 hydrogen bonds)
  • Anti-parallel strands - One runs 5’→3’, the other 3’→5’
  • Sugar-phosphate backbone - Provides structural support

DNA Replication#

DNA replication is the process by which a cell copies its DNA before cell division. It’s semi-conservative, meaning each new DNA molecule contains one original strand and one newly synthesised strand.

The Replication Process#

  1. Enzyme Breakdown

    • DNA helicase breaks hydrogen bonds between base pairs, unwinding the double helix
    • This creates a replication fork - a Y-shaped region where strands separate
  2. Primer Binding

    • RNA primase creates short RNA primers complementary to the DNA template
    • Primers provide a starting point for DNA polymerase
  3. Strand Synthesis

    • Leading strand: Synthesised continuously 5’→3’ towards the replication fork by DNA polymerase III
    • Lagging strand: Synthesised discontinuously in fragments (Okazaki fragments) 5’→3’ away from the fork
  4. Joining and Proofreading

    • DNA polymerase I removes RNA primers and replaces them with DNA
    • DNA ligase joins Okazaki fragments on the lagging strand
    • DNA polymerase has proofreading activity - checks and corrects mismatched bases
IMPORTANT

The 5’→3’ direction is crucial because DNA polymerase can only add nucleotides to the 3’ end of a growing strand.

Why Semi-Conservative?#

The semi-conservative nature of DNA replication was proven by the Meselson-Stahl experiment (1958):

GenerationDNA TypeDensity
0 (Parent)¹⁵N-¹⁵NHeavy
1¹⁵N-¹⁴NIntermediate
2¹⁵N-¹⁴N and ¹⁴N-¹⁴NIntermediate + Light

This evidence showed that each new DNA molecule contained one original (heavy) strand and one new (light) strand.

Transcription - DNA to mRNA#

Transcription is the process of creating a complementary RNA copy of a DNA sequence.

Key Steps#

  1. Initiation

    • RNA polymerase binds to the promoter region upstream of the gene
    • DNA unwinds at the transcription start site
  2. Elongation

    • RNA polymerase moves along the template strand 3’→5’
    • Synthesises mRNA 5’→3’ (complementary to DNA, with U instead of T)
    • The coding strand has the same sequence as mRNA (except T→U)
  3. Termination

    • RNA polymerase reaches a terminator sequence
    • mRNA transcript is released
    • DNA rewinds

Post-Transcriptional Modification#

In eukaryotes, the primary transcript undergoes processing:

  • Splicing - Introns (non-coding regions) are removed, exons (coding regions) are joined
  • 5’ Capping - A modified guanine nucleotide is added to protect mRNA
  • 3’ Poly-A Tail - Multiple adenine nucleotides added for stability and export
NOTE

Alternative splicing allows a single gene to produce multiple proteins - explaining how humans have ~20,000 genes but ~100,000+ proteins!

Translation - mRNA to Protein#

Translation is the synthesis of proteins from mRNA codons.

The Players#

ComponentFunction
mRNACarries genetic code from nucleus to ribosome
tRNATransports specific amino acids to ribosome
RibosomeSite of protein synthesis (composed of rRNA + proteins)
Amino acidsBuilding blocks of proteins

The Process#

  1. Initiation

    • Ribosome binds to mRNA at the 5’ end
    • Scans for the start codon (AUG) coding for methionine
    • First tRNA carries methionine to the P site
  2. Elongation

    • tRNA carries amino acid to A site based on codon-anticodon matching
    • Peptide bond forms between amino acids (catalysed by peptidyl transferase)
    • Ribosome translocates - tRNA moves to P site, then E site to exit
    • Process repeats, building the polypeptide chain
  3. Termination

    • Ribosome reaches a stop codon (UAA, UAG, or UGA)
    • Release factor binds, causing polypeptide release
    • Ribosome subunits separate

The Genetic Code#

The genetic code is:

  • Degenerate - Multiple codons can code for the same amino acid
  • Non-overlapping - Codons are read sequentially without overlap
  • Universal - Nearly all organisms use the same code (evidence for common ancestry)
TIP

A helpful mnemonic for amino acids: “All Teachers Have Great Books” = Alanine, Threonine, Histidine, Glycine… (create your own!)

Key Exam Points for AQA#

IMPORTANT

Common exam questions often focus on:

  • Comparing DNA and RNA structure
  • The roles of enzymes in replication and protein synthesis
  • Why semi-conservative replication is important
  • Calculating base percentages using Chargaff’s rules (A=T, C=G)

Practice Question#

If a DNA molecule has 20% adenine, what percentage of guanine does it contain?

Show Answer

Since A pairs with T: A = T = 20% Total A + T = 40% Remaining G + C = 60% Since G = C: G = 30%

Summary#

The central dogma explains how genetic information flows:

  • DNA replication ensures genetic information is passed to daughter cells
  • Transcription converts DNA to mRNA for export from the nucleus
  • Translation decodes mRNA to synthesize proteins

Understanding these processes is fundamental to genetics, biotechnology, and medicine. From gene therapy to PCR technology, the applications are endless!


Next up: Protein Structure and Enzyme Function - Understanding how DNA codes for functional proteins.

DNA Replication and the Central Dogma
https://shannonrufus.com/posts/dna-replication-and-the-central-dogma/
Author
Shannon Rufus
Published at
2024-09-15
License
CC BY-NC-SA 4.0

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