BMB 462 Lecture 19 Outline of Last Lecture I Sources of atoms for de novo synthesis II Function and Defects of Phosphoribosyltransferases III Defects in Nucleotide Breakdown IV Nucleoside mono di and tri phosphate conversion V Ribonucleotide Reductase VI dNTP Synthesis VII Thymidylate Synthesis VIII Inhibition of dNTP Synthesis Outline of Current Lecture I Function of DNA and RNA II DNA Carries the Cell s Genetic Information III Primary DNA Structure IV The History of DNA Determining Secondary Structure Current Lecture Concepts to remembers from previous courses lectures I Function of DNA and RNA a DNA DNA is information storage i It provides info to cell stored as DNA and then can be transmitted as RNA through the cell to make proteins ii It passes the info on to progeny when the cell divides via replication DNA replicates itself so that there is a copy for each daughter cell b RNA i More diverse functions ii Functions as information carrier in the form of mRNA made when you transcribed then translated into protein iii Acts as an adapter tRNA adapter between mRNA and amino acids during translation These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute iv Stores information i e in some viral genomes v Structural integral part of ribosome structure vi Catalysis in ribosomes there are some rRNAs that catalyze reactions form ribozymes some functions used to be carried out by RNA and only later did the functions transfer to proteins vii Regulation miRNA micro RNAs regulate gene expression by regulating either transcription or translation Believe they re involved in a lot of cancers siRNA small inhibitory RNAs work with inhibiting certain gene expression viii Splicing snRNA small nuclear RNA II DNA Carries the Cell s Genetic Information a DNA stores information in its linear sequence of nucleotides and codes for proteins via RNA rRNA b Passing information on to progeny 2 processes in cell replication mitosis creates new cells done by all somatic body cells and meiosis only done by gametes sex cells for reproduction i Information can be transferred because the DNA is double stranded The information is then retained due to many mechanisms working to minimize change in the sequence c DNA Information maintained by Repair Mechanisms i Many mechanisms minimizing change use base pairing for repair 1 Mismatch repair 2 Nucleotide excision repair 3 Base excision repair ii These mechanisms all recognize mutations in DNA and carry out various processes of fixing them iii The cell spends a lot of energy to keep its DNA information intact d Process of Using DNA as information i Have the info in the double stranded DNA the cell uses that to get the mRNA Then you get a polypeptide and then the polypeptide is folded into its 3D structure 1 The making and folding of the polypeptide often happens simultaneously ii Information is used to make proteins and RNA if you were to change the information sequence you could change the function of the protein or completely destroy it 1 Change in protein function is used by evolution to create new phenotypes a i e change in DNA sequence can alter an enzyme s specificity or efficiency e Example of Evolution of DNA i In yeast there was a gene for a hexokinase that used glucose as a substrate ii A mutation occurred in the duplication of the original glucose hexokinase gene still had one copy of the original strand that could operate under the original function so evolutionary mutations could work on the other strand to create a mutant gene that changed the substrate specificity of the protein to galactose instead of glucose 1 Now yeast has two kinases one specific for glucose and one specific for galactose change of the gene caused a change in substrate specificity iii Change needs to be minimal to preserve function some change is required to produce variation for evolution III Primary DNA Structure a Primary Structure relates to the sequence of nucleotides linked by phosphodiester bonds i DNA is written 5 to 3 and built 3 to 5 5 end has the phosphate the 3 end has the OH ii The base order then stores the information iii Phosphodiester bonds occur because the 3 end can attack the phosphate on a new nucleotide group and link the molecules together b Stability of DNA i DNA is more stable than RNA because RNA has an OH group on the 2 carbon which makes it unstable Under slightly alkaline conditions that extra OH can be attacked and forms a cyclic intermediate 2 3 cyclic monophosphate derivative and the RNA starts to be degraded 1 This difference in stability may be the reason why DNA and not RNA is the main information carrier IV The History of DNA Determining Secondary Structure a 1868 Friedrich Miescher isolated DNA for the first time b The structure of DNA was discovered 1940 by Avery MacLeod and McCarthy i Avery determined DNA was the genetic information by making a strain of Streptococcus pneumoniae virulent again but people did not believe that DNA was the information carrier due to the fact that DNA only has 4 bases whereas proteins have 20 amino acids and have multiple functions and that better explained the variability of genes c Chargaff s Rules for Base Pairing i Different species have different ratios of the bases of A T G C varies between species but within one species the ratios are the same 1 They are fixed in one species in one individual and in all the different tissues ii He also noticed that A T and G C and that A G T C the purines the pyrimidines d Structure from Rosalind Franklin s X ray Diffraction i Watson and Crick knew about the ratios of bases but it was Franklin s image of DNA that really led them to figure out the structure 1 She was a crystallographer 2 Figured out that DNA has a helical structure due to noticing repeats of 34 angstroms 3 4nm and of 3 4 ii Realized the structure would only function if the phosphates had to point outside with the bases inside others i e Watson thought it was reversed iii Scandal She had a collaborator Wilkins who shared her data with Watson without her knowledge Watson and Crick took the information and made the double helix discovery 1 Watson Crick and Wilkins got credit Franklin didn t 2 They got the noble prize but she was already dead at that point e Watson and Crick s Model i Repeating Structures 1 Periodicity of 3 4 the distance of 1 base pair to the next 2 34 one helical turn her measures were a little
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