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Genetic Regulation


Dogma of molecular biology
Mind Map by pau.leal10, updated more than 1 year ago
Created by pau.leal10 over 6 years ago

Resource summary

Genetic Regulation
  1. DNA: Desoxirribonucleic Acid
    1. Polymere of Nucleotides
      1. Watson & Crick's Model
        1. Double Helix Structure
          1. Back Bone (outside): Sugar + Phosphate
            1. (inside) Paired Bases
              1. Double Ring: Purine Bases
                1. Adenine (A)
                  1. Guanine (G)
                  2. Single Ring: Pyrimidine Bases
                    1. Thymine (T)
                      1. Cytosine (C)
                        1. Chargaff's Rules
                          1. 1. the amount of A, T, G, C in DNA varies from specie to specie
                            1. 2. in each species the amount of A=T and the amount of G=C
                              1. Structure
                                1. COMPLEMENTARY PAIRING: A is always bonded to T & G is always bonded to C by a hydrogen bond
                                  1. A purine (wide) is always paired to a pyrimidine (narrow) to complement sizes
                                    1. Strands with ANTI PARALLEL ARRANGEMENT
                                      1. Every nucleotide has a phosphate group at the 5' position of the sugar & they bind together by linking this 5' phosphate to the free hydroxyl (--OH) at the 3' position of the other nucleotide's sugar (giving it it's direction)
                                        1. DOGMA OF MOLECULAR BIOLOGY
                                          1. Replication: Copying a DNA molecule
                                            1. DNA replication is termed semi-conservative replication because each daughter DNA double helix contains an old strand from the parental DNA double helix and a new strand
                                              1. STEPS:
                                                1. 1. Unwinding: an enzyme called helicase breaks the hydrogen bond between the paired bases (creating a replication fork)
                                                  1. 2. Complementary Base Pairing: New complementary nucleotides, always present in the nucleus, are positioned in place (by an enzyme complex called DNA polymerase)
                                                    1. 3. Joining: new strands are crated so each daughter DNA molecule contains an old and a new strand (by an enzyme complex called DNA polymerase)
                                                      1. DNA ligase, joins the fragments, but there is no way for DNA polymerase to replicate the 5' ends of both new strands after RNA primers are removed. So DNA molecules get shorter as one replication follows another.
                                                      2. the leading new strand continues it's normal process, the lagging strand is discontinuous, the segments are known as Okazaki Fragments. as the RNA primers are replaced by the nucleotides.
                                                        1. A DNA polymerase is very accurate and makes a mistake approximately once per 100,000 base pairs at most.
                                                      3. Differences between...
                                                        1. Eukaryotes
                                                          1. Telomeres (special nucleotide sequence at the end of the DNA) do not code for proteins, instead creates repeats of a short nucleotide sequence, such as TTAGGG.
                                                            1. replication may begin at numerous origins
                                                              1. the process can take hours because of the amount of info replicated
                                                              2. Prokaryotes
                                                                1. Bacteria have a single circular loop of DNA, replication moves around the DNA molecule in one direction only.
                                                                  1. it requires 40 min. to replicate & can do so every 20 min.
                                                                    1. it is possible for a new round of DNA replication to begin even before the previous round is complete.
                                                              3. Transcription
                                                                1. 1st step in syntetization of a protein: DNA serves as a template for RNA formation.
                                                                  1. pre-mRNA if formed (by RNA Polymerase when it ataches to a DNA promoter)
                                                                    1. RNA (Ribonucleic Acid) carries the information
                                                                      1. Polymere composed of nucleotides: sugar ribose & bases.
                                                                        1. Structure: single stranded, NO double helix
                                                                          1. typically has a poly a tail (has many adenine nucleotides at one end & a cap at the other end)
                                                                          2. Adenine (A), Guanine (G), Uracil (U), Cytosine (C)
                                                                            1. Types of RNA
                                                                              1. Messenger RNA (mRNA) takes a message from DNA in the nucleus to the ribosomes in the cytoplasm.
                                                                                1. Transfer RNA (tRNA) transfers amino acids to the ribosomes
                                                                                  1. Ribosomal RNA (rRNA), along with ribosomal proteins, makes up the ribosomes, where polypeptides are synthesized.
                                                                                2. Codon (triplet code): 3 nucleotide bases
                                                                                  1. properties
                                                                                    1. 1. The genetic code is degenerate. most amino acids have more than one codon; (leucine, serine, and arginine have six different codons)
                                                                                      1. The degeneracy of the code protects against potentially harmful effects of mutations.
                                                                                      2. 2. The genetic code is unambiguous. Each triplet codon has only one meaning.
                                                                                        1. 3. The code has 1 start and 3 stop signals.
                                                                                    2. elongation of the mRNA continues until DNA reaches a stop point & the mRNA is liberated = mRNA Transcript
                                                                                      1. made up of nucleotides & regions called: exons and introns
                                                                                        1. splicing: introns are removed (forming an mRNA: template to form proteins)
                                                                                          1. m RNA will leave the nucleus through the nuclear pore into the cell's cytoplasm
                                                                                            1. Prokatyotes have self-spllicing: the intron itself has the capability of enzymatically splicing itself out of a premRNA.
                                                                                              1. Another type of RNA called small nucleolar RNA (snoRNA) is present in the nucleolus, where it helps process rRNA and tRNA molecules.
                                                                                              2. Eukaryotes: splicing is done by spliceosomes, which contain small nuclear RNAs (snRNAs: are capable of identifying the introns to be removed) A spliceosome utilizes a ribozyme when it removes the introns.
                                                                                        2. REGULATION OF GENE ACTIVITY
                                                                                          1. Prokaryote Regulation
                                                                                            1. Operon Model
                                                                                              1. Promoter: signals where transcription is to begin.
                                                                                                1. Operator: controls transcription of structural genes.
                                                                                                  1. active repressor binds to the operator, RNA polymerase cannot attach to the promoter, and transcription cannot occur
                                                                                                  2. Structural Genes: instructions to primary structure of enzymes in a metabolic pathway
                                                                                                    1. Regulator Gene: codes for a repressor that controls whether the operon is active or not.
                                                                                                      1. Trp Operon (repressible system)
                                                                                                        1. when the active repressor binds to the operator transcription is prevented because RNA polymerase can't bind to the promoter
                                                                                                          1. gene expression "on" by default the corepressor can bind to the repressor activating it causing expresion to go off
                                                                                                            1. only on/off (negative gene regulation)
                                                                                                            2. Lac Operon (inducible systems)
                                                                                                              1. on/ off (negative gene regulation)
                                                                                                                1. gene expression "off" by default corepressor binds to repressor deactivating it and turnig expresion "on" by unbinding it form the operator
                                                                                                                  1. by unbinding the repressor from the promoter expression is allowed
                                                                                                                  2. up/ down (positive gene regulation)
                                                                                                                    1. there are no repressors, just activators
                                                                                                                      1. there's some level of transcription but we need more
                                                                                                                        1. cyclic amp activates the activator by binding to it and changing it's form so it can bind with the promoter and increase transctription
                                                                                                                  3. Eukaryote Regulation
                                                                                                                    1. 1. Chromatin Structure
                                                                                                                      1. core of 8 histone proteins wraped around by DNA
                                                                                                                        1. the DNA packed around the histone can't be transcribed
                                                                                                                          1. chromatin remodeling complex can liberate the DNA making it transcribable
                                                                                                                            1. Heterochromatin: strongly packed histones
                                                                                                                              1. Euchromatin: loosely packed histones
                                                                                                                                1. Epigenetic inheritance: When histones are methylated, sometimes the DNA itself becomes methylated as well = genetic imprinting, expression depends if the gene is inherited from the mother or father, not the gene it self
                                                                                                                                2. 2. Transcriptional Control
                                                                                                                                  1. transcription factors: proteins that help regulate transcription
                                                                                                                                    1. transcription activators are DNA binding proteins that speed transcription dramatically.
                                                                                                                                      1. transcription factors bind to the promoter and transcription activators bind to an enhancer when the loop is formed to allow transcription to begin
                                                                                                                                    2. 3. Posttranscriptional Control
                                                                                                                                      1. occurs in the nucleus and includes alternative mRNA splicing and controlling the speed with which mRNA leaves the nucleus.
                                                                                                                                        1. pre-mRNA has introns and exons, introns stay in the nucleus as exons exit the nucleous = mRNA
                                                                                                                                      2. 4. Translational Control
                                                                                                                                        1. mRNA strands after splicing are too short so they become...
                                                                                                                                          1. micro RNA's, they are double stranded and where turned off, micro RNA can lower the expression of genes
                                                                                                                                        2. 5. Posttranslational Control
                                                                                                                                          1. the last chance a cell has for influencing gene expression
                                                                                                                                            1. Some proteins are not immediately active after synthesis.
                                                                                                                                              1. some proteins only become active when it is appropriate for them to do so.
                                                                                                                                        3. Gene Mutations
                                                                                                                                          1. permanent change in the sequence of bases in DNA
                                                                                                                                            1. Causes
                                                                                                                                              1. Spontaneous mutations
                                                                                                                                                1. the movement of transposons from one chromosomal location to another can disrupt a gene and lead to an abnormal product.
                                                                                                                                                  1. a base in DNA can undergo a chemical change that leads to a miss pairing during replication and may be carried in future generations.
                                                                                                                                                    1. they are extremely rare, 1 billion nucleotide pairs replicated.
                                                                                                                                                    2. Induced Mutations
                                                                                                                                                      1. caused by mutagens, environmental factors that can alter the base composition of DNA
                                                                                                                                                        1. Many mutagens are also carcinogens (cancer-causing)
                                                                                                                                                          1. industrial chemicals, foods, tabacco, radiation
                                                                                                                                                      2. Effects
                                                                                                                                                        1. on Protein Activity
                                                                                                                                                          1. point mutation: e a change in a single DNA nucleo - tide and, therefore, a possible change in a specific amino acid.
                                                                                                                                                            1. can range in effect, depending on the particular codon change
                                                                                                                                                            2. Frameshift mutation: one or more nucleotides are either inserted or deleted from DNA.
                                                                                                                                                              1. The result can be a completely new sequence of codons and nonfunctional protein
                                                                                                                                                                1. Non-Functional Proteins
                                                                                                                                                                  1. dramatic effect on the phenotype, because enzymes are often a part of metabolic pathways.
                                                                                                                                                                    1. Mental retardation, albinism, PKU, etc.
                                                                                                                                                            3. Cancer
                                                                                                                                                              1. The development of cancer involves a series of accumulating mutations that can be different for each type of cancer
                                                                                                                                                                1. tumor suppressor genes are inactive and oncogenes are active
                                                                                                                                                                  1. cell division occurs uncontrollably because a cell signaling pathway that reaches from the plasma membrane to the nucleus no longer functions as it should
                                                                                                                                                        2. Translation
                                                                                                                                                          1. 2nd step in syntetization of a protein: the mRNA transcript directs the sequence of amino acids in a polypeptide.
                                                                                                                                                            1. cell changes a nucleotide sequence into an amino acid sequence. With the help of the three types of RNA, a gene (a segment of DNA) specifies the sequence of amino acids in a polypeptide
                                                                                                                                                            2. A tRNA molecule is a single-stranded nucleic acid that doubles back on itself to create regions where complementary bases are hydrogen-bonded to one another
                                                                                                                                                              1. there's at least 1 for every amino acid in the protein, it binds to the 3' end.
                                                                                                                                                                1. on the 5' end, an anti codon (group of three bases complementary to a specific mRNA codon so that they pair in an antiparallel fashion)
                                                                                                                                                                  1. fewer tRNAs that codos because of the wobble hypothesis.
                                                                                                                                                                    1. the first two positions in a tRNA anticodon pair obey the A–U/G–C configuration, but the third position can be variable. This helps ensure that despite changes in DNA base sequences, the correct sequence of amino acids will result in a protein
                                                                                                                                                                  2. aminoacyl-tRNA synthetase (enzyme found in the cytoplasm) attaches a different type of aminoacid to the specific tRNA
                                                                                                                                                                    1. this process uses ATP
                                                                                                                                                                      1. amino acid–tRNA complex is formed
                                                                                                                                                                        1. travels to a ribosome
                                                                                                                                                                          1. formation in eukaryotes: rRNA spliced to form 2 rRNA strtands, 1 small & 1 big
                                                                                                                                                                            1. produced from a DNA template in the nucleolus of a nucleus, synthetised by RNA polymerase I
                                                                                                                                                                              1. they leave the nucleolus & fold to form a small and large sub unit of the ribosome = pre-ribosome (still inside the nucleus)
                                                                                                                                                                                1. they leave the nucleous and the ribosome can either stay un the cytoplasm or get attatchd to the ER
                                                                                                                                                                              2. the small and large sub units of the ribosome attach to the cap of the mRNA
                                                                                                                                                                                1. Translation begins
                                                                                                                                                                                  1. STAGE 1 Initiation: Proteins (initiation factors) assemble the small ribosomal subunit and the large ribosomal subunit through the P site of the ribosome, now occupied by the initiator tRNA (with an attached peptide), to the cap of the mRNA
                                                                                                                                                                                    1. In prokaryotes, a small ribosomal subunit attaches to the mRNA in the vicinity of the start codon (AUG).The first or initiator tRNA pairs with this codon. Then, a large ribosomal subunit joins to the small subunit
                                                                                                                                                                                      1. STAGE 2 Elongation:
                                                                                                                                                                                        1. 1 tRNA + amino acid arrives at the A site.
                                                                                                                                                                                          1. 2 ribosome verifies that new tRNA matches the codon and firmly places it at the A site, peptide will transfer to the new tRNA.
                                                                                                                                                                                            1. 3 the peptide bond formation is one amino acid longer than it was before. creating a protein. (now attached to the new tRNA at A site)
                                                                                                                                                                                              1. 4 translocation occurs: The ribosome moves forward, and the peptide-bearing tRNA is now at the P site of the ribosome. The spent tRNA is now at the E site, and it exits. :A new codon is at the A site and is ready to receive another tRNA. (this process repeats until the end of mRNA strand)
                                                                                                                                                                                                1. STAGE 3 Termination: it occurs at a stop codon (codon that don't code for an amino acid), a protein called a release factor, binded to a stop codon, releases the tRNA at P site and the polypeptide chain. the ribosome separates into 2,
                                                                                                                                                                                          2. structure: ribosome has three binding sites for tRNAs.
                                                                                                                                                                                            1. E (exit) site
                                                                                                                                                                                              1. P (peptide) site
                                                                                                                                                                                                1. A (amino acid) site
                                                                                                                                                                                          3. DNA synthesised by RNA polymerase III creates the tRNA
                                                                                                                                                                                        2. The universal nature of the genetic code provides strong evidence that all living things share a common evolutionary heritage
                                                                                                                                                                                          1. . Since the same genetic code is used by all living things, it is possible to transfer genes from one organism to another.
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