Central Dogma of Molecular Biology

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Central Dogma of Molecular Biology The central dogma of molecular biology is an explanation of the flow of genetic information within a biological system. It describes the two-step process, transcription and translation, by which the information in genes flows from DNA to RNA to make proteins. Francis Crick: "The central dogma of molecular biology deals with the detailed residue-by-residue transfer of sequential information. It states that such information cannot be transferred back from protein to either protein or nucleic acid." Summary of Processes: DNA $\rightarrow$ RNA $\rightarrow$ Protein Replication: DNA makes copies of itself. Transcription: DNA is transcribed into RNA. Translation: RNA is translated into protein. DNA Replication Transcription RNA Translation Protein 1. DNA (Deoxyribonucleic Acid) Definition: A double-stranded helical molecule that contains the instructions an organism needs to develop, live, and reproduce. One of the four major types of macromolecules essential for all forms of life. Structure: Double helix, often described as a "twisted ladder." Discovered by James Watson and Francis Crick in 1953 (Nobel Prize in 1962). Comparing DNA and RNA Feature DNA RNA Sugar Deoxyribose Ribose Bases A, T, C, G A, U, C, G Strands Double-stranded (ds) Single-stranded (ss) Location in cell Nucleus Cytoplasm Function Carrier of genetic information Encoder/decoder of genetic information Catalytic role Non-catalytic Catalytic (e.g., enzymes) 2. DNA Replication (DNA Synthesis) The biological process of producing two identical replicas of DNA from one original DNA molecule. This process occurs in all living organisms and is the basis for biological inheritance. Semi-conservative replication: Each new DNA molecule consists of one original strand and one newly synthesized strand. The DNA double helix is anti-parallel , meaning the two strands run in opposite 5' to 3' directions. The double helix unwounds, and each strand acts as a template for synthesizing new partner strands. Bases are matched (A with T, C with G). Carried out by DNA polymerase . DNA can be opened up to create templates for copying: Single-stranded DNA can serve as a template for high-fidelity replication. Also serves as a template for making mRNA (transcription). 3. Transcription (RNA Synthesis) The process by which the information contained in a section of DNA is replicated in the form of a newly assembled piece of messenger RNA (mRNA). Differs from DNA synthesis in that only one strand of DNA, the template strand , is used to make mRNA. Carried out by RNA polymerase . Types of RNA Type of RNA Function mRNA (messenger RNA) Carries genetic information from DNA to ribosomes for protein synthesis (code for proteins). rRNA (ribosomal RNA) Forms part of the structure of the ribosome and participates in protein synthesis. tRNA (transfer RNA) Acts as an adaptor molecule in protein synthesis, carrying specific amino acids to the ribosome. Small RNAs Involved in pre-mRNA splicing, transport of proteins to the ER, and other cellular processes. Stages of Transcription Initiation: RNA polymerase binds to the promoter sequence in duplex DNA, forming a "closed complex." Polymerase melts duplex DNA near the transcription start site, forming a transcription bubble ("open complex"). Polymerase catalyzes phosphodiester linkage of two initial rNTPs. Elongation: Polymerase advances 3' $\rightarrow$ 5' down the template strand, melting duplex DNA and adding rNTPs to growing RNA. A DNA-RNA hybrid region forms temporarily. Termination: At the transcription stop site, polymerase releases completed RNA and dissociates from DNA. 4. Translation (Protein Synthesis) The mRNA formed in transcription is transported out of the nucleus into the cytoplasm, to the ribosome. Here, it directs protein synthesis with the assistance of tRNA. Performed on ribosomes . tRNA molecules bind to the two binding sites of the ribosome, and by hydrogen bonding to the mRNA. A peptide bond forms between two amino acids to make a dipeptide, while the tRNA molecule is left uncharged. The uncharged tRNA molecule leaves the ribosome, while the ribosome moves one codon to the right. Another tRNA molecule binds, and a peptide bond forms between the two amino acids to make a tripeptide. Proteins Proteins are the end products of the central dogma. Protein synthesis involves building a peptide chain using tRNAs to add amino acids and mRNA as a blueprint for the specific sequence. For proteins to function, they must fold into the correct three-dimensional shape and be targeted to the correct part of the cell. A protein is a chain of amino acids. There are twenty common amino acids. Amino acids have unique electrostatic and chemical properties. There are energetically favorable ways amino acid chains can fold. The Genetic Code The genetic code refers to the rules by which information encoded in genetic material (DNA or RNA sequences) is translated into proteins. Triplet: The code is read in triplets of nucleotides (codons). Unpunctuated and non-overlapping: The codons are read consecutively without gaps or overlaps. Degenerate: Most amino acids are specified by more than one codon. Only Methionine (Met) and Tryptophan (Trp) are specified by a single codon. Unambiguous: Each codon specifies only one amino acid. Universal: The genetic code is largely the same across all organisms, with minor exceptions. Genetic Code Table (mRNA codons) Second Base First Base (5' end) U C A G Third Base (3' end) U UUU (Phe) UCU (Ser) UAU (Tyr) UGU (Cys) U UUC (Phe) UCC (Ser) UAC (Tyr) UGC (Cys) C UUA (Leu) UCA (Ser) UAA (STOP) UGA (STOP) A UUG (Leu) UCG (Ser) UAG (STOP) UGG (Trp) G C CUU (Leu) CCU (Pro) CAU (His) CGU (Arg) U CUC (Leu) CCC (Pro) CAC (His) CGC (Arg) C CUA (Leu) CCA (Pro) CAA (Gln) CGA (Arg) A CUG (Leu) CCG (Pro) CAG (Gln) CGG (Arg) G A AUU (Ile) ACU (Thr) AAU (Asn) AGU (Ser) U AUC (Ile) ACC (Thr) AAC (Asn) AGC (Ser) C AUA (Ile) ACA (Thr) AAA (Lys) AGA (Arg) A AUG (Met, START) ACG (Thr) AAG (Lys) AGG (Arg) G G GUU (Val) GCU (Ala) GAU (Asp) GGU (Gly) U GUC (Val) GCC (Ala) GAC (Asp) GGC (Gly) C GUA (Val) GCA (Ala) GAA (Glu) GGA (Gly) A GUG (Val) GCG (Ala) GAG (Glu) GGG (Gly) G Practice Problems Given the DNA template strand: T G C C G A A C G T C G T A C What is the complementary DNA strand? What is the complementary RNA strand? Using the genetic code, what would the amino acid chain be?