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UW-Milwaukee CHEM 501 - Genes and Chromosomes

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Chemistry 501 Handout 24 Genes and Chromosomes Chapter 24Slide 2Slide 3Slide 4Slide 5Slide 6Slide 7Slide 8Slide 9Slide 10Slide 11Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19Slide 20Slide 21Slide 22Slide 23Slide 24Slide 25Slide 26Slide 27Slide 28Slide 29Slide 30Slide 31Slide 32Slide 33Slide 34Slide 35Slide 36Slide 37Slide 38Slide 39Slide 40Chemistry 501 Handout 24 Genes and ChromosomesChapter 24Dep. of Chemistry & BiochemistryProf. IndigLehninger. Principles of Biochemistry.by Nelson and Cox, 5th Edition; W.H. Freeman and CompanyColinearity of the coding nucleotide sequences of DNA and mRNA and the amino acid sequence of a polypeptide chain.codonDNA molecules are much longer than the cellular or viral packages that contain themDNA from a lysed E.coli cellEukaryotic ChromosomesSister chromatidsA dividing mitochondrionThe mtDNA is replicated each time the mitochondrion dividesIntrons in two eukaryotic genesTypes of sequences in the human genomeLong interspersed elements6 to 8 kbp(encode enzymes for transposition)Short interspersed elements100 to 300 bp1.5 to 11 kbpSimple sequence repeatsLarge segmentalduplicationsImportant structural elements of a yeast chromosomecentromereSupercoiling of DNASupercoiling induced by separating the strandsof a helical structureRelaxed and supercoiled plasmid DNAsMost cellular DNA is underwound DNA underwinding is definedby topological linking number84 bpLinking number applied to closed-circular DNA moleculesNegative and positivesupercoils2,100 bp underwinding overwinding = Lk/Lk0 = -2/200 = -0.011% of the helical turns present in theDNA (in its B form) has been removedSuperhelical densitytopoisomersLinking number can be broken down into two structural componentsTwist (Tw) and Writhe (Wr)Measure of the coiling of thehelix axisLocal twisting or spatialrelationship of neighboringbase pairLk = Tw + WrIn addition of causing supercoiling and making strand separation somewhat easier,the underwinding of DNA facilitates structural changes in the moleculefacilitates the partial strand separation needed to promotecruciform formation at appropriate sequencesTopoisomerases catalyze changes in the linking number of DNAType 1(t)Type 1: single strand breaks;changes Lk in increments of 1Type 2: double strand breaks;changes Lk in increments of 2Bacterial type 1 topoisomerase alter linking numberGenerally relax DNA by removing negative supercoils(increasing Lk)Proposed mechanism for the alteration of linking number by eukaryotic type IIA topoisomeraseTwo ATPs are bound and hydrolyzed during this cycleWithout topoisomerases, cells cannot replicate or package their DNA, or express their genes, and they die.They are important drug targets for bacterial infections and cancerantibioticsChemotherapeutic agentsTopoisomerase inhibitors are important pharmaceutical agentsPlectonemic supercoilingDNA compaction requires a special form of supercoilingThe supercoils are right-handed in a negatively supercoiled DNA molecule, and theytend to be extended and narrow rather than compacted, often with multiple branches.DNA compaction requires a special form of supercoilingSame DNA molecule, drawn in scale Solenoidal supercoilingprovides a much greater degree of compaction(tight left-handed turns)Chromatin assemblyHistone cores do not bind randomly to DNA; rather, they tend to position themselves at certain locationsIn some cases seems todepend on a local abundance of A=T base pairs in the DNAhelix where it is in contact with the histoneThe structure of chromosomesThe chromosomal material, chromatin, consists of DNA and proteins.NucleosomesBeginning with nucleosomes, eukaryotic chromosomal DNAis packed in a sucession ofhigher-order structures thatultimately yield the compactchromosomeNucleosomes are thefundamental organizational unit of chromatinbeads-in-a-stringDNA wrapped around the nucleosome coreEight histone proteinsTwo of each: H2A, H2B, H3, and H4Top view Side viewNucleosome with 146 bp of bound DNAThe DNA binds in a left-handed solenoidal supercoil that circumnavigates the histone complex 1.8 timesHistone complexThe 30 nm fiber, a higher-order organization of nucleosomes.Loops of chromosomal DNA attached to a nuclear scaffold.Compaction of DNA in a eukaryotic chromosome.DNA compaction in eukaryotes is likely to involve coils upon coilsupon coils….Next level of organization(after 30 nm fiber)Structure of SMC proteins.(Structural Maintenance of Chromosomes)also bound to additional regulatory proteins (not shown)Model for the roles of cohesins and condensins during the eukaryotic cell cycle.E. coli nucleoids.Looped domains of the E. coli chromosome.Bacterial DNA is also highly organized.Changes in chromosome structure during the eukaryotic cell cycleA partially unraveled human chromosome, revealing numerous loops of DNA attached to a scaffoldlike structure.Several variants of histones H3, H2A, and H2B are knownHistone-fold domain (common to all core histones)Sites of Lys/Arg residue methylation and Ser phosphorylation are indicatedInformation that is passed from one generation to another but is not encoded in DNA is referred to as epigenetic information.Much of it is in the form of covalent modification of histones and/or placement of histone variants in chromosomeChIP-chip experiment designed to reveal the genomic DNA sequences to which a particular histone variant binds.The pattern of hybridization on the microarray reveals the DNA sequences bound by the nucleosomes with the histone


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