Lecture 7 - Chapter 3 (1) PDF

Module II – Flow of Genetic Information Chapter 3 – Fundamentals of Molecular Biology (Genes & DNA) Chapter 5 – DNA Replication Chapter 5 – DNA Repair Chapter 6 – Transcription Chapter 6 – RNA Processing Chapter 8 – Translation Chapter 7/8 – Transcriptional & Post-Transcriptional Regulation...

Module II – Flow of Genetic Information Chapter 3 – Fundamentals of Molecular Biology (Genes & DNA) Chapter 5 – DNA Replication Chapter 5 – DNA Repair Chapter 6 – Transcription Chapter 6 – RNA Processing Chapter 8 – Translation Chapter 7/8 – Transcriptional & Post-Transcriptional Regulation Exam 2 – Tuesday, October 15th Fundamentals of Molecular Biology Chapter 3 Section 3.1 and 3.2 Learning Objectives Explain the relationship between genes and chromosomes. Summarize and interpret the experiments that established DNA as the genetic material. Diagram the structure of DNA and relate it to its function. Summarize and interpret the experimental evidence for semi- conservative replication. --------------------------------------------------------------------------------------------- Describe the roles of mRNA, tRNA, and rRNA in protein synthesis Predict the effects of specific mutations on the amino acid sequence of an encoded protein. Describe reverse transcription. Molecular Biology Key Concepts Genes are carried on chromosomes, with DNA as the genetic material Complementary base pairing drives DNA structure, semi-conservative replication, and transcription of mRNA mRNA codons are translated into amino acids of polypeptides through tRNA as an intermediary rRNA, tRNA, and reverse transcriptase are all exceptions to the Central Dogma Historical Context of The Central Dogma & Molecular Biology Chromosome Theory of Inheritance What is the genetic material that explains Mendel’s principles of inheritance? What is the structure of DNA? Historical Context of The Central Dogma & Molecular Biology What connects genes and proteins? The Molecular Revolution and Molecular Medicine Chromosome Theory of Inheritance Genes are found at specific locations on chromosomes Sperm-producing parent Egg-producing parent The behavior of chromosomes during meiosis can explain Mendel’s laws of inheritance. Diploid Haploid Gene Allele Identifying DNA as the genetic material 1920s – Fred Griffith; British medical officer studying Streptococcus pneumoniae (pneumococcus) – S strain – _____________ – R strain – _____________ Main conclusion? Identifying DNA as the genetic material 15 years later, Oswald Avery along with Colin MacLeod and Maclyn McCarty individually test ability of molecules to transform _____________ R-strain cells into ______________ S-strain cells Note Check – join.nearpod.com code: Which of the following treatments would result in a LOSS of the ability to transform R strain cells into S strain cells? a) RNase b) Protease c) DNase d) Lipase e) Amylase NOTE CHECK Identifying DNA as the genetic material 15 years later, Oswald Avery along with Colin MacLeod and Maclyn McCarty individually test ability of molecules to transform nonlethal R-strain cells into lethal S-strain cells Work published in 1944 received little attention. Main conclusion?  Identifying DNA as the genetic material Debate was settled in 1952 by Alfred Hershey and Martha Chase working with T2 viruses Main conclusion? The structure of DNA: four nucleotide building blocks Individual nucleotides are joined together by a _____________________ bond between the _______________________ group on one nucleotide and the _______________________ group on the next nucleotide. The structure of DNA: a functional molecule A DNA molecule consists of two __________________ chains of nucleotides arranged in an __________________________ orientation twisted into a _____________________________ shape The structure of DNA: four nucleotide building blocks The two strands of the DNA double helix are held together by _________________________ between ____________________________ _________________. Note Check – join.nearpod.com code: The DNA double helix can be denatured into single strands when heated. Which of these DNA sequences would you expect to be part of the double- stranded molecule that would denature at the lowest melting temperature? a)ATGCATAAATTGATA b)GTACGATATTTACGC NOTE CHECK c)CGGCTGCATGCAGCT d)GTCAGTATCGAGCCG  1953 – Watson & Crick published the double helical model for DNA structure “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.” Structure = Function How does complementary base pairing provide a clue about DNA’s replication? There were three possible models for DNA replication: Meselson and Stahl’s experiment to determine type of replication Note Check: join.nearpod.com enter code Based on the results shown, which model of DNA replication is correct? a) Semi-conservative b) Conservative c) Dispersive NOTE CHECK _____________________ replication of DNA SECTION 3.2 EXPRESSION OF GENETIC INFORMATION The Central Dogma The Central Dogma, but in reality rRNA m tRNA Case study: Genetic Cause of Tay Sachs Disease Inherited neurological disorder caused by malfunction of an enzyme called hexosaminidase A (HexA), which is responsible for breaking down fatty substances Buildup of fat in the brain results in loss of neurodevelopment, seizures, and death by age 4 Especially prevalent in Ashkenazi Flotte et al. 2022 Jewish populations Transcription of the wild-type (normal) HexA gene This is a segment of DNA sequence from the HexA gene: 5’ ATGTGGGGCGAATAT 3’ [non-template] NOTE CHECK 3’ TACACCCCGCTTATA 5’ [template] What is the mRNA sequence that would result when this is transcribed? a) 5’ ATGTGGGGCGAATAT 3’ b) 5’ TACACCCCGCTTATA 3’ c) 5’ AUGUGGGGCGAAUAU 3’ d) 5’ AUAUUCGCCCCACAU 3’ Join.nearpod.com pin = The genetic code: Translating mRNA into protein Here is the transcript from this section of the HexA gene: 5’ AUGUGGGGCGAAUAU 3’ What is the peptide sequence that would result when this is translated? a) Met-Trp-Gly-Glu-Tyr b) Tyr-Glu-Gly-Trp-Met c) Tyr-Lys-Arg-Gly-Leu d) Leu-Gly-Arg-Lys-Tyr NOTE CHECK Join.nearpod.com pin = Common mutation found in HexA gene in Tay Sachs patients One common mutation found in Tay Sachs patients is called E482K – this means that amino acid #482 is normally E Join.nearpod.com pin = (glu) but is mutated to K (lys) in some Tay Sachs patients. Here again is the mRNA transcript for this segment of HexA, with the codon for E482 underlined: 5’ AUGUGGGGCGAAUAU 3’ Which of the following mutations (shown in the mRNA transcript) would be most likely to result in the E482K mutation in a Tay Sachs patient? a) 5’ AUGUGGGGCGACUAU 3’ b) 5’ AUGUGGGGCAAGUAU 3’ NOTE CHECK c) 5’ AUGUGGGGCGAGUAU 3’ d) 5’ AUGUGGGGCAAAUAU 3’ Reverse Transcription and Retrovirus Replication Retroviruses are an exception to the Central Dogma Can retroviruses be used to insert normal HexA genes in Tay Sachs patient genomes? Why might retroviruses *not* be the ideal gene therapy system? Dziaková et al. 2016 Summary: Fundamentals of Molecular Biology Genes are carried on chromosomes, with DNA as the genetic material Complementary base pairing drives DNA structure, semi- conservative replication, and transcription of mRNA mRNA codons are translated into amino acids of polypeptides through tRNA as an intermediary rRNA, tRNA, and reverse transcriptase are all exceptions to the Central Dogma