BIO105: DNA, Gene Regulation, and Cancer

DNA, Gene Regulation, and Cancer

• This lecture introduces DNA as the primary heritable molecule.
• Sets the stage for Chapters 17 and 18:
  • Chapter 17: Protein Synthesis
    • How ribosomes use mRNA to build proteins like insulin or ATP synthase.
  • Chapter 18: Gene Regulation & Totipotency
    • All cells have the same DNA, but only some genes are turned on.
    • Selective expression is gene regulation.
    • Explains how totipotent cells can specialize.
• Cancer Case: DNA translocation causes a problem:
  • Collagen gene promoter (normally active in skin) fused with the PDGF gene’s transcription unit (normally active in bone marrow).
  • Skin cells produce and secrete PDGF, causing uncontrolled cell division and skin cancer.
• All genes are made of DNA and have two main parts:
  • Promoter: controls when and where a gene is active.
  • Transcription Unit: gets copied into RNA, which can become a protein.
• This mutation shows why understanding molecular genetics and gene regulation is important for understanding diseases like cancer.

DNA Structure, Gene Regulation, and Inheritance

• Expands on how genes are structured and how their organization affects function and inheritance.
• Every gene is made of:
  1. Promoter:
     • Regulatory region.
     • Controls when, where, and how much of the gene is expressed.
  2. Transcription Unit:
     • The part of the gene, which gets copied into RNA and used to make a protein.
• Cancer case discussed:
  • A collagen promoter (normally active in skin) fused to the PDGF transcription unit (usually active in bone marrow).
  • Result: PDGF is now made in skin cells, causing uncontrolled cell division → skin cancer.
• This mutation could be:
  • Inherited (runs in the family), or
  • Acquired (e.g. UV damage from sun exposure).
• DNA as a Physical Molecule
  • DNA is a linear molecule made of nucleotides (A, G, C, T for DNA; A, G, C, U for RNA).
  • Genes are like very long words in a book with no spaces.
  • Promoters and transcription units are like regulatory switches and instructions, respectively.
• Genotype vs. Phenotype
  • Genotype = the full set of genetic instructions you inherit from your parents.
  • Phenotype = how those instructions play out in your body (what you physically express).
  • In diploid cells, one copy comes from mom and one from dad; both can contribute to the final protein output.
• Example:
  • Aquaporin channels made from both mom’s and dad’s DNA determine how well water flows through your cells.
  • If mom’s copy works and dad’s doesn’t, you may get ~50% function, which could be okay or harmful—depends on the gene.
• Gene Expression Process
  1. DNA → (transcription) → RNA
  2. RNA → (translation) → Protein
  • Transcription (in nucleus) = regulated by the promoter (Chapter 18)
  • Translation (in cytoplasm by ribosomes) = builds the protein (Chapter 17)
• Modern Genetics Tools
  • Scientists use DNA sequencing to read and search entire genomes (e.g. finding the insulin gene in pigs).
  • DNA databases allow researchers to explore the structure and mutations of genes across species.

Gene Structure, Mutation, and Gene Regulation

• Gene Structure Overview:
  • Every gene has two main parts:
    1. Promoter: regulates when, where, and how much of the gene is expressed.
    2. Transcription Unit: the part of DNA that gets transcribed into RNA and used to make proteins.
• Mutation and Misexpression Example:
  • In some cancers, like skin cancer, a mutation can accidentally link the promoter of one gene (e.g., skin collagen) to the transcription unit of another (e.g., PDGF).
  • This leads to PDGF being produced in skin cells where it shouldn’t be, stimulating abnormal cell growth.
  • This can be inherited or caused by external damage (like UV rays).
• Exons and Introns:
  • Within the transcription unit, coding regions are made up of exons.
  • Introns are extra sequences removed during RNA processing.
  • Only exons are used to make proteins.
• Gene Regulation:
  • The promoter includes a proximal and distal region, both made of DNA.
  • Transcription begins when transcription factors bind to the promoter and recruit RNA polymerase.
  • RNA polymerase then synthesizes RNA from the transcription unit.
• Scientific Use of Gene Fusion:
  • Scientists can intentionally fuse promoters and genes from different species to study gene expression.
  • Example: A jellyfish GFP gene was combined with a mouse promoter to make certain mouse cells glow, helping track specific cells (like germline cells).
• Key Takeaways:
  • Genes are physical, linear pieces of DNA made of letter sequences (A, G, C, T).
  • The coding region within the transcription unit dictates the amino acid sequence of proteins.
  • DNA is inherited from both parents (genotype), and its expression determines the traits we observe (phenotype).
  • Gene expression is a regulated process involving promoter regions, transcription factors, and RNA polymerase.

Chapter 17: Translation (Protein Synthesis)

• Purpose:
  • Provides a basic framework for how proteins are made from mRNA at the ribosome — a process called translation.
  1. Location & Process Flow
     • Transcription happens in the nucleus, producing mRNA from DNA.
     • Translation happens in the cytoplasm, where ribosomes use mRNA to make proteins.
  2. Key Terms and Structures
     • mRNA (messenger RNA): Carries instructions from DNA.
     • Ribosome: The site of protein synthesis.
     • Codon: A sequence of three RNA bases that codes for one amino acid.
     • tRNA (transfer RNA): Brings amino acids to the ribosome. Has an anticodon that pairs with the mRNA codon.
     • Aminoacyl tRNA synthetase: Enzyme that connects the correct amino acid to its tRNA.
  3. Ribosome Sites
     • A Site (Acceptor): New tRNA with amino acid enters.
     • P Site (Peptidyl): Holds the growing protein chain.
     • E Site (Exit): tRNA exits after delivering its amino acid.
  4. Genetic Code
     • 64 codons total:
       • 61 codons specify amino acids.
       • 3 codons signal “stop” (end of translation).
     • The ribosome reads codons one at a time, adding corresponding amino acids to the protein.
  5. Translation Cycle
     1. Ribosome reads a codon at the A site.
     2. tRNA binds via its anticodon and adds an amino acid.
     3. The ribosome shifts:
        • A → P → E
        • New codon enters A site.
     4. tRNAs recycle and repeat the cycle.
     5. The process stops at a stop codon.
  6. Summary
     • Translation uses the mRNA template to build a specific amino acid chain (protein).
     • This is how genetic information becomes a functional product.
     • Chapter 17 focuses on this entire process and how the genetic code directs it.

Chapter 18: Gene Expression & Transcription

• Key Focus
  • Builds on Chapter 17 (translation at ribosome).
  • Now shifting focus to transcription in the nucleus — how genes are turned on or off.
• DNA: Same in Every Cell, Expression Varies
  • All cells have the same DNA, but different genes are active in different cells.
    • Example: The insulin gene exists in all cells but is only expressed in pancreas cells.
• Promoters and Transcription Factors
  • Promoter: A DNA sequence that acts like a landing pad for proteins.
  • Transcription Factors (TFs): Proteins that bind to the promoter and help turn genes on/off by:
    • Recruiting RNA polymerase, which starts transcribing DNA into RNA.
• Structure of a Gene
  • Gene contains:
    • Promoter Region (upstream):
      • Proximal Promoter: Close to the gene. Shows RNA polymerase where to bind.
      • Distal Promoter: Further away. Binds transcription factors that regulate activity.
    • Transcription Unit:
      • Includes the coding region (has codons that ribosomes later use to build proteins).
• Transcription Overview
  • RNA Polymerase binds to the promoter (with help from TFs).
  • It reads the DNA template and synthesizes RNA.
  • This RNA later gets translated into protein in the cytoplasm.
• Analogy: Flashlight in the Dark
  • Think of DNA like a book in the dark:
    • It’s unreadable until a transcription factor (the flashlight) binds to the promoter.
    • Once “lit,” RNA polymerase can read the nearby gene and transcribe it.
• Example: Hormone Activation
  • Testosterone can bind to a receptor (a TF).
  • This receptor/TF binds to a gene’s promoter, activating genes involved in growth during adolescence.
• Gene Misregulation (Mutation Example)
  • A mutation can move a gene near the wrong promoter.
    • Ex: A skin gene promoter accidentally placed in front of a growth gene (PDGF).
    • TFs for skin now accidentally activate PDGF, possibly leading to cancer.
• Takeaway
  • Gene expression is tightly controlled by where and when RNA polymerase can bind.
  • This is regulated by transcription factors binding to promoter regions like flipping switches in different cells.