Molecular Biology of the Gene : where the genetic information is stored, blueprint for making proteins. RNA: Always involved in protein synthesis Macromolecules (polymers!) Monomers (units): nucleotides Nitrogenous base Cytosine Ribose (RNA) Triphosphate group 5-carbon sugar Guanine Adenine Deoxiribose () Thymine Uracil RNA Central dogma: Set of ideas describing how the cell uses the information stored in the transcription Makes a copy of in the form of RNA Synthesizes proteins using as template Proteins Structural Carrier, Enzymes, Hormones, antibodies 1
Accepted as the heritable material in 1952 TWO strands with helical disposition. One strands is the code, the other help to protect the coding strand backbone: sugar and phosphate sequence bases: 1) Hydrogen bonds between them attach one strand to the other. 2) arranged in a specific format, always is 3 H bonds: 2 H bonds: Cytosine Adenine C A G T Guanine Thymine Bases store the genetic information! and chromosomes arranges together with specific proteins called histones Chromatin fibers are + histones Before cell division Condensed chromatin fibers Are replicated Two copies of each molecule The condensed chromatin are the chromosomes Single strand Chromatin ( with histones) Chromosome (1) double strand (2) Chromatin strand ( with histones). (3) Chromatin during interphase (mitosis) with centromere. (4) Condensed chromatin during prophase (mitosis). (Two copies of the molecules are now present) (5) Chromosomes during mitosis/meiosis 2
Replication: occurs (in the nucleus) in cells in preparation for cell division (1) Break of H bonds (2) (3) Strands are separated Copy in both directions New nucleotides are added by the enzyme Combination of the different replication sites (4) (1) An enzyme breaks H bonds between nitrogenous bases (2) Strands are separated and both are copied (two directions copy!) (3) Enzyme sequentially attaches new nucleotides with dehydration reactions (4) Replication bubbles combine and two new strands complementary to the original ones are formed Controlling gene expression Which strand of must be used for transcription? When to stop making RNA? Where must transcription (RNA generation) begin? rr rr rr rr Promoter region Sequence recognized by the RNA polymerase Gene Termination region Marks the end of transcription Regulatory Regions (rr): Specific proteins called transcription factors attach to these parts making the promoter region more o less visible to the RNA polymerase Splicing Posttranscriptional changes in the RNA only in eukaryotes protein-coding region is non continuous and pieces of noncoding RNA (introns) are removed after tanscription. Only exons (meaningful information) remain 3
RNA ONE strand backbone: sugar and phosphate sequence bases: arranged in a specific Cytosine C format, always Adenine A G U Guanine Uracil Three types of RNA: all copies of parts of strands 1) : messenger RNA, carries the genetic information from the cell nucleus to the cytoplasm 2) trna: transfer RNA, transfers or carries amino acids to the ribosomes, and aids in the pairing of amino acids 3) rrna: ribosomal RNA, covered in protein to form a ribosome, where the protein synthesis () takes place Transcription trna transcription rrna (ribosomes) Proteins language to RNA language Using a template to synthesize RNA Takes place in the nucleus Why a copy? The original library remains safe, no risks of getting the damaged or destroyed The two strands of are separated and the bases of the coding strand exposed The coding strand is read only in one direction RNA polymerase Nucleotides Available in the nucleus Dehydration synthesis reactions bonding of nucleotides and construction of a single strand of RNA, trna, rrna 4
Translation transcription RNA language to protein language Using a template to synthesize proteins trna rrna (ribosomes) Proteins How does the cell machinery know which amino acid goes with each part of RNA? Codon (3 bases code) UGU = Cystine The dictionary! The code in the is used to direct the sequential assembly of amino acids in the cytoplasm Sequence of nitrogenous bases: each combination of 3 bases (called codon) in the defines un amino acid, trna, rrna The factory! The translator! Translate the code to the amino acid language and transports the aminoacids The trna has bases (named anticodon) that match codon of the with the correct amino acid Where to begin and end? The signal is present in the! STOP! 3 specific codons are used to indicate STOP! Termination of the process START! Only one codon is the initiator Start of the process 5
Protein synthesis An enzyme catalyzes the synthesis dehydration reaction After the bonding took place, the trna detaches from the amino acid and leaves ribosome A new trna with an amino acid approximates to the ribosome aa trna codon START! ribosome A trna with an amino acid (aa) is present at the ribosome, a second trna arrives with another amino acid STOP! When a stop codon is found in the code stops final chain Proteins that work in the cytoplasm are synthesized in free cytoplasmatic ribosomes Proteins for export or destined to be part of the cell membrane are synthesized on ribosomes attached to the endoplasmic reticulum (ER). Ribosomes disassembles can be used again Mutations Any change in the nucleotide sequence of Normal sequence Kind of mutation MISSENSE (nucleotide) NONSENSE (stop) FRAMESHIFT Due to INSERTION (nucleotide) Due to DELETION (nucleotide) DELETION (codon=3 bases) INSERTION (codon=3 bases) EXPANDING MUTATION PARENTS CHILDREN GRANDCHILDREN THE ONE BIG FLY HAS ONE RED EYE sequence change THQ ONE BIG FLY HAS ONE RED EYE THE ONE BIG THE ONE QBI GFL YHA DON ERE DEY E TEO NEB IGF LYH ASO NER EDE YE THE ONE BIG FLY HAS ONE RED EYE THE ONE BIG WET FLY HAS ONE RED EYE THE ONE BIG FLY HAS ONE RED EYE THE ONE BIG FLY HAS HAS ONE RED EYE THE ONE BIG FLY HAS HAS HAS HAS ONE R Some mutations results are silent Mutation happen, but the new codon codifies for the same amino acid changes but protein is the same Mutagenic agents Substances or conditions that cause to change (viruses, X-rays, UV light) Some mutations result in changes in the final protein Hemoglobin: 145 amino acids (aa) in four chains. A missense mutation (one nucleotide) changes one aa hemoglobin shape changes when oxygen levels are low Irregular shape causes hemoglobin to clump, blocking the blood vessels no oxygen delivering weakness, brain damage, rheumatism In which cells is a mutation potentially more dangerous? Sexual cells! Cells used for reproduction 6