HBG 22 ( Transcription)

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    • Transcription is the process of making an RNA copy from DNA
    • Transcription starts at a specific DNA sequence (TATAA) that serves as an attachment site for transcription molecules
    • RNA polymerase synthesizes RNA from DNA template and binds to recognition sites in the promoter region
    • RNA polymerase synthesizes RNA from 5' - 3' direction and does not need a dNTP template to start
    • RNA polymerase continues to untwist the DNA while extending the RNA molecule
    • Terminator sequence signals that the RNA transcript is complete and the RNA transcript is released from the RNA polymerase
    • At the end of transcription, mRNA is not ready for translation but is ready for translation into protein after post-transcriptional processing
    • Toxins can interfere with transcription by binding to RNA polymerase II and inhibiting its action in cells
    • Post-transcriptional processing involves converting pre-mRNA transcript into mature mRNA
    • Forms of modification in post-transcriptional processing include 5' capping, 3' polyadenylation, and splicing
    • Addition of a modified guanine nucleotide at the 5' end of mRNA protects the transcript and assists in ribosome attachment during translation
    • Polyadenylation stabilizes the transcript, helps in transcription termination, and regulates nuclear transport
    • Introns are non-coding areas in mRNA that are removed during splicing, leaving only exons that encode for proteins
    • Splicing of introns is done by the spliceosome, which also glues the exons together to form a mature mRNA
    • Translation is the process by which ribosomes use the information in mRNA to synthesize proteins
    • tRNA transfers specific amino acids to a growing polypeptide chain at the ribosomal site of protein synthesis
    • Ribosomes, composed of rRNA and ribosomal proteins, translate mRNA into proteins by reading the codons and adding amino acids
    • The translation process continues until a stop codon enters the A site, then release factor enzymes add a water molecule to the last amino acid of the chain
    • Gene regulation controls and regulates the expression of genes
    • Factors that regulate gene expression include external signals, internal signals, and protein signals from other cells
    • There are five levels of gene expression control: Genomic Level Control, Transcriptional Level Control, RNA Processing & Nuclear Transport Control, Translational Level Control, and Post-Translational Processing
    • Epigenetics refers to changes in phenotype or gene expression caused by mechanisms other than changes in the DNA sequence, and these changes can be inherited
    • In Medicine, gene expression and regulation play a crucial role in diseases like COVID-19 and Alzheimer's
    • COVID-19 vaccine development involves transcription and translation of the COVID-19 virus spike gene
    • Alzheimer's disease is linked to epigenetic changes like hypomethylation of the promoter region of Amyloid Precursor Protein (APP) and Tau protein gene
    • Cancer involves the loss of epigenetic control, such as hypomethylation of proto-oncogenes and hypermethylation of tumor suppressor genes (TSGs)
    • Mechanisms controlling DNA methylation can be imperfect, leading to cancer progression by the loss of tumor suppressor genes through promoter methylation
    • Epigenetic drugs are used in cancer treatment to reverse aberrant methylation of genes
    • Cell Cycle
      1. G1 phase - Cell growth
      2. S phase (synthesis) - DNA synthesis occur
      3. G2 phase - Growth and Mitosis preparation
    • For Meiosis, the process is doubled compared to Mitosis
    • DNA Replication Characteristics
      • Act like photocopy machine lah tbh
      • Occur before the cells divide
      • Each strand of DNA molecule is template to produce parent-identical complementary strand
      • Known as semi-conservative replication
      • Able to copy 50 base pairs/second
    • DNA Replication Process
      1. Replication starts from 5’ to 3’ direction
      2. Starts at replication origin
      3. Unwinds the helix by DNA helicase (helped by ATP)
      4. Multiples of opening; replication fork (Y-shaped part) formed
      5. SSB prevents/remains the strand from being coiled/folded again
      6. Primase catalyzes synthesis of the short RNA primer that is complementary to the template itself
      7. DNA Polymerase III extends the chains
    • Enzymes involved in DNA Replication
      • DNA Helicase - unzipping enzymes
      • Primase - the starter/indicator
      • DNA Polymerase - the builder
      • DNA Ligase - the gluer
    • Limitation during DNA Replication: Need assistance of primer to solve limitations
    • First limitation: Synthesizing new DNA strand from 5’ to 3’ direction
    • Second limitation: DNA polymerase will not synthesize DNA from one of the single strands (lagging strand) as it starts from 5’ end first
    • RNA primer = filler
    • Type of DNA strands
      • Leading strand
      • Lagging strand (Okazaki fragments)
    • DNA Ligase
      Glue; connecting one Okazaki fragment to another
    • Topoisomerases remove helical twists by cutting the strand and resealing the cut
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