Skip to Main Content

1. OVERVIEW

  1. Similar to DNA structure and synthesis, these subjects are closely related to Hematology/Oncology and Microbiology sections

  2. Thus, much of the focus is, as usual, on pharm and key disease applications (e.g., sickle cell anemia)

  3. In addition, 2 Biochemistry-specific topics that tend to show up on Step 1: Collagen synthesis and the lac operon

2. REGULATION OF GENE EXPRESSION

  1. There are several ways gene expression is regulated

    1. Initiation requires transcription factor binding to promoters (directly upstream of the gene)

      • Promoters are often cell-type specific

      • TATA and CAAT boxes are common features of promoters

    2. Expression is regulated by enhancers and silencers (anywhere around the gene)

    3. Methylation of DNA (CpG islands) mutes expression (see Chapter 2)

    4. Histone modification also regulates expression

      • Methylation of histones usually mutes expression

      • Acetylation of histones activates expression

  2. The lac operon is the example Step 1 likes to use to integrate these concepts

    1. Set of co-expressed genes used by bacteria to activate lactose metabolism when lactose is available and glucose is not

    2. Two regulatory steps must occur together to express the lac operon

      • Low glucose—activates CAP (binds enhancer)

      • High lactose—removes repressor protein (binds repressor)

  3. Mutations that disrupt gene regulation can be just as damaging as mutations in the gene's protein-coding region

    1. Protein deficiencies

      • In beta-thalassemia, mutations can occur in the promoter → less production of functional protein

      • Clinical: Anemia, hemolysis, weakness/fatigue

    2. Increased activity

      • Myc is a transcription factor that controls cell proliferation

      • Burkitt lymphoma, an aggressive form of cancer more common in children → caused by chromosomal translocation causing constitutive Myc expression

      • Clinical: Rapidly growing tumors on the jaw/face (endemic variant) or abdomen (sporadic); tumor lysis, hyperuricemia

3. TRANSCRIPTION

  1. Four major types of RNA are found in the cell

    1. Ribosomal RNA (rRNA) is part of the ribosome, the main actor in translation

      • Synthesized by RNA polymerase I

    2. Messenger RNA (mRNA) encodes protein sequences

      • Synthesized by RNA polymerase II

      • Processed from heteronuclear RNA initially synthesized from DNA sequence in the nucleus

      • Amatoxins (poisonous mushrooms) inhibit RNA Pol II → apoptosis

    3. Transfer RNA (tRNA) links each mRNA codon into its corresponding amino acid

      • Synthesized by RNA polymerase III

    4. Micro RNA (miRNA) are short RNA sequences that do not encode protein

      • Regulates expression of proteins

      • Binds mRNA and prevents translation and/or tags for degradation

  2. RNA is processed to become mRNA

    1. Poly-adenylation tails and 7-methylguanosine triphosphate caps are added ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.