Genetics - 06 Central Dogma of Genetics

HUMAN GENETICS AND CYTOGENETICS Comparison DNA CENTRAL DOGMA OF GENETICS INTRODUCTION • • • Deoxyribonucleic Acid (DNA) is a genetic material of all living organisms on Earth. o It is double helix, antiparallel and held together by hydrogen bonds between the complementary bases. o The structure provides the basis for storing and expressing genetic information coded by the 4 nitrogen bases. RNA which is the genetic material of viruses has many similarities to DNA except that it is single stranded and its sugar and uracil base is not present in DNA. The process of replication, transcription and translation are the necessary processes for gene expression. Ultraviolet Damage LESSON 1: DNA AS A GENETIC MATERIAL • • DNA VS. RNA Comparison Name Function Structural Features DNA Deoxyribonucleic Acid Long-term storage of genetic information; transmission of genetic information to make other cells and new organisms. B-form double helix. DNA is a doublestranded molecule consisting of a long chain of nucleotides. Composition of Bases and Sugars deoxyribose sugar; phosphate backbone; adenine, guanine, cytosine, thymine bases Propagation DNA is selfreplicating. Base Pairing AT (adeninethymine) GC (guaninecytosine) The C-H bonds in DNA make it fairly stable, plus the body destroys enzymes that would attack DNA. The small grooves in the helix also serve as protection, providing minimal space for enzymes to attach. Reactivity RNA Ribonucleic Acid Used to transfer the genetic code from the nucleus to the ribosomes to make proteins. RNA is used to transmit genetic information in some organisms and may have been the molecule used to store genetic blueprints in primitive organisms. A-form helix. RNA usually is a singlestrand helix consisting of shorter chains of nucleotides. ribose sugar; phosphate backbone; adenine, guanine, cytosine, uracil bases RNA is synthesized from DNA on an asneeded basis. AU (adenine-uracil) GC (guaninecytosine) The O-H bond in the ribose of RNA makes the molecule more reactive, compared with DNA. RNA is not stable under alkaline conditions, plus the large grooves in the molecule make it susceptible to enzyme attack. RNA is constantly DNA is susceptible to UV damage. RNA produced, used, degraded, and recycled. Compared with DNA, RNA is relatively resistant to UV damage. There were several scientists who contributed to the discovery of DNA as a genetic material. Various experiments were done to discover its structure and composition. DNA is made up of a polymer of nucleotides comprising of phosphate, deoxyribose sugar and nitrogen bases o Nitrogenous bases ▪ Purine - Adenine and guanine ▪ Pyrimidine - cytosine and thymine THE STRUCTURE OF THE DNA • • • • • • • • • • dsDNA - double stranded o Most common o B-form DNA Each strand is a nucleotide o Sugar ▪ Deoxyribose ▪ Make DNA, deoxynucleotide o Phosphate ▪ Connects by phosphodiester bonds 5' to 3' o Nitrogenous base ▪ Always attached at 1' of sugar Orientation difference o Top strand - 5' → 3' o Bottom strand - 3' → 5' o Antiparallelism (Watson-Crick model) Two strand connect through covalent hydrogen bods o Connects by base pairs o CG - 3 H bonds o AT - 2 H bonds Pyrimidines - CT Purines - AT Geometry is the same to allow stacking Each turn is approximately 10 base pairs Major grove - base pair specific Minor groove base pair non-specific LESSON 2: DNA REPLICATION • • DNA replication happen inside the nucleus during the Sphase of the cell cycle, having another double helix DNA as its by product. Several enzymes like helicase, primase, ligase etc. are necessary in order to unwind the DNA strand and produce a new strand identical to the original one. o Helicase - unwind double helix structure of DNA by denaturation o Ligase - seals off the DNA fragments o DNA polymerase - main synthesis enzyme, for elongation o Primase - starting point for synthesis o Exonuclease - removes the RNA primer • • The structure of the DNA, its antiparallel orientation makes the process of replication possible. Why is there a need to replicate the DNA of the cell? Remember that every cell will undergo cell division thus to maintain the amount of DNA per cell, replication must happen before any division must occur. LESSON 4: TRANSLATION: BUILDING OF POLYPEPTIDE • DNA REPLICATION • • • • • The first step in DNA replication is to separate the two strands. This unzipping is done by an enzyme called helicase o Helicase - form replication fork The separated strands each provide a template for creating a new strand of DNA. o Primase - starts process ▪ Makes a small piece of primer An enzyme called DNA polymerase binds to the primer and will make the new strand of DNA. DNA polymerase can only add DNA bases in one direction, from the 5' end to the 3' end. o Leading strand - continuously made o Lagging strand - discontinuous due to opposite direction o Okazaki fragments - segments of DNA ▪ Start with DNA primer ▪ DNA polymerase add a few DNA bases ▪ Next primer is added Once the new DNA has been made the enzyme exonuclease removes all the RNA primers from both strands of DNA. Another DNA polymerase enzyme then fills in the gaps that are left behind with DNA. o Exonuclease - remove all primer Finally, the enzyme DNA ligase seals up the fragments of DNA in both strands to form a continuous double strand. o Ligase - fills up the gaps DNA replication is described as semi- conservative because each DNA molecule is made up of one old, conserved strand of DNA and one new one. • • LESSON 5: CONTROL OF GENE EXPRESSION • • LESSON 3: TRANSCRIPTION: MAKING OF MATURED MRNA • • Transcription is the process that follows after the process of replication. o It is defined as the decoding of information from DNA to RNA. o This also happen inside the nucleus of every eukaryotic cell. o The end product of transcription is the messenger RNA which must undergo processing to become a matured mRNA ready to be migrated via the nuclear pores to the ribosomes in the cytoplasm. How important is this process? Remember that DNA is the carrier of genetic information which we inherited from our parents, however they are a permanent “resident” of the nucleus thus decoding is important so as to make a template for the process of protein synthesis that will happen in the cytoplasm. There are 3 types of RNA that are necessary for the process of translation: Messenger RNA; Transfer RNA and ribosomal RNA. Each type have different structure and considered as bridge between gene and protein. o Messenger RNA (mRNA) ▪ Is a copy of the information carried by a gene on the DNA ▪ The role of mRNA is to move the information contained in DNA to the translation machinery o Transfer RNA (tRNA) ▪ The information adapter molecule that carries its specific amino acid to the site of protein synthesis o Ribosomal RNA (rRNA) ▪ A component of the ribosomes, the protein synthetic factories in the cell These 3 types of RNA must be present during the initiation, elongation and termination part of translation. The end product of translation is a chain of amino acids, called polypeptide chain. The genetic code is needed to decipher what amino acid are coded by the codons which is the original mRNA copied from the DNA. This is the end of the Central Dogma of Molecular Genetics. After translation which is also called as protein synthesis several kinds of amino acid will be formed which will later undergo protein folding to be used as protein necessary in the different tissues and organs formation. • • • • • After translation protein must fold into one or more specific conformations in order to function. Various proteins assist in the precise folding, misfolded proteins are sent out to endoplasmic reticulum, tagged by ubiquitin and some will be taken to a cellular garbage disposal called proteasome. Gene Expression is a process by which information from gene is used in the synthesis of a functional gene products. o This expression of genetic information is regulated by mechanism that exert control over transcription, mRNA stability, translation and other post translational modification. o Expression of gene at the wrong time, in a wrong cell type or in abnormal amount can lead to cancer or cell death even when the gene is normal. Mutation is change in DNA sequence brought about by different mutagens. o It can occur at the DNA level substituting one DNA base or adding or deleting few bases or at chromosome level. o The effects vary, either can stop or slow down the production of protein or in some cases can over produce the protein or can impair the protein’s function. Individuals may vary in the degree to which a particular gene is expressed. This variability is because of the differences in DNA sequence as well as the differences in the process of transcription. Histones play an importance role in chromatin remodeling. They can on or off the process of transcription thus control what protein will be express or not. RNA interferences can also control gene expression.