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Topics Nucleic Acids: structure and function DNA RNA Organization of the genome Protein Synthesis (genetic expression) Transcription Translation Mutations Post-transcriptional modification epigenetics DNA: Structure and Function DNA Function genetic information how to build, operate, and repair cell Specifically how and when to make proteins passed from one cell generation to the next; from parent to child (gametes/sex cells) From one cell to the next within an individual DNA Structure long chains of nucleotides Nucleotide = sugar + phosphate + nitrogenous base Sugar = deoxyribose (5C) 4 Different Bases: A, T, G, C Bases = pyrimidines (1 ring) or purines (2 rings) sugar-phosphate backbone=covalent base-base=hydrogen hydrogen bond 3’ DNA Structure Cont.: Double Helix double stranded 5’ Twisted=helix covalent bond 5’ 3’ ‘f’-five; ‘f’ phosphate; 5’ end DNA Structure Cont.: Complementary Base Pairing 4 different bases Complementary pairing C—G A—T Functional Characteristics of DNA: IMPORTANT!! Information = order of the bases/base sequence ATTGCGCA Different sequencesdifferent meaning/info (proteins) ATTGCGGA Complementary base pairing Allows DNA to be copied over and over and the information stays the same. Importance of base-pairing A A T A T T T A T A T T A T A C C G C G G G C G C C C G C G G G C G C A A T A T T T A T A Importance of base-pairing continued A T T A T A T T A A T A T A T A A T A T A C G G C G C G G C C G C G C C G G C G C G G C C G C G C A T T A T A T T A A T A T A DNA Organization DNA molecule = genes + regulatory DNA + “other” “chromosome” ~3% of DNA non-coding: ~97% of DNA gene =protein instructions 20-25k estimated genes (but >100,000 estimated proteins….problem…..) regulatory = when to activate gene/make a protein e.g., transcription factors such as hormones can bind regulatory DNA and signal a gene to be used Regulates when protein is made (gene activated) Protein building instructions (gene) DNA Organization DNA is wrapped around histone (a protein) DNA + Histone = Chromatin Chromatin histone 3-31 DNA Organization: Histone and access to genes Histone is important in making genes accessible (usable) or inaccesible (non-usable) If DNA can’t be accessesgene can’t be used (no protein) If DNA can be accessedgene can be used when needed Histone can control which/if genes can be used=Epigenetics acetylation allows access deacetylation shuts off/prevents access methylation prevents access/shuts off demethylation allows access/shuts off and others………. Chromatin continued Condensed chromatin: transcription factors can’t get to regulatory DNA to activate gene use acetylation and demethylation Open/loose structure allows transcription factors to access DNA and initiate gene use deacetylation and methylation and methylation Condensed chromatin: inaccessible 3-33 REPLICATION: duplication of DNA as part of cell division DNA Replication Happens as part of cell cycle In preparation for cell division Duplicates all the DNA: 1 copy 2 copies One copy for each cell Semiconservative G C G C G C C G C G C G G C G C G C A T A T A T T A T A T A Errors in replication mutations (i.e. a change in genetic information/DNA sequence) 1 copy of DNA 1 copy of all DNA 2 copy of All DNA 1 copy of DNA Replication of DNA Parent/mother cell • Mitosis divides/separate daughter cells: the each one two copies identical of copy of all the DNA: genetically identical identical to the mother cell chromosomes • Cytokinesis divides up the cytoplasm contents DNA Replication DNA helicase “unzips” the DNA New nucleotides are added/paired with the existing strands DNA polymerase binds the new nucleotides together creating the P-S backbone Result is two identical DNA molecules (i.e., the base sequence is the same) Genetic Expression Proteins Synthesis: how dna is used to make functional proteins Genetic Expression: from DNA to cell function/structure DNA mRNA Proteins cell function/structure •structure •transport •contraction •receptors •cell ID •hormones/signaling Protein Synthesis: making proteins from DNA Transcription= DNA mRNA (in nucleus) 2. Translation = mRNA Protein (in cytoplasm @ ribosome) 1. Nucleic Acids - RNA Single stranded chains of nucleotides Sugar = ribose Bases and Pairing G, C, A, U replaces T G-C T-A or A (dna) –U (rna) types of RNA (made from DNA): Messenger RNA – mRNA Transfer RNA – tRNA Ribosomal RNA – rRNA others (siRNA, miRNA, RNA based enzymes, etc) 2-59 Transcription: from DNA mRNA Transcription Begins: When Transcription factors (e.g., hormones) bind DNA transcripition starts/is initiated RNA polymerase binds to a “start” sequence/codon & unzips DNA promoter = how much transcription RNA Polymerase moves down template strand complimentary RNA bases bind DNA RNA nucleotides bind together (via RNA poly) at end of gene mRNA detaches and RNA poly detaches DNA zips up when transcription is done Post-transcriptional modification 3-35 Transcription Template strand Coding strand 3-36 Transcription mRNA: a copy of the information on a gene Created by transcription Single strand of nucleotides Phosphate, ribose sugar, bases U instead of T Codons = 3-base groups One codon is a “start” codon Three codons are “stop codons” Each of the remaining 60 codons corresponds to an amino acid tRNA Single stranded piece of RNA tRNA carries and delivers amino acids to mRNA/ribosome tRNA anticodon binds to mRNA codon complementary Each tRNA carries a specific amino acid that corresponds to its anticodon 3-44 Protein Synthesis and the Genetic Code DNA template strand 3-43 Mutations, DNA, and Protiens Mutation = change in DNA base sequence change in protien change in structure and/or function Basic Types of Mutations Point mutations substitution insertion frame-shift mutations deletion Point Mutations Substitution: ATT GCG AGT TAT CCG ATT GCG AGT TAG CCG Insertion: ATT GCG AGT TAT CCG ATT GCG TAG TTA TCC G Deletion ATT GCG AGT TAT CCG ATT GCG GTT ATC CG A frameshifts Base Sequences and Human Variation SNP’s (single nucleotide polymorphisms) single nucleotide differences in the DNA between different individuals responsible for most differences in appearance and physiology ATT GCG ATC CGA TAT TTT AAC CCC ATA CGG TAT TTT TCG ATT GCG TTC CGA TAT TTT AAC CCC ATA CGG TAT TTT TCG ATT GCG ATC CGA TAT TTG AAC CCC ATA CGG TAT TTT TCG ATT GCC ATC CGA TAT TTT AAC CCC ATA CGG TAA TTT TCG ATT GCC ATC CGA TAT TTT CAC CCC ATA CGG TAT TTT TCG ATT GCG ATC CGA TAT TTT CAC CCC ATA CGG TAA TTT TCG RNA Synthesis & Post-transciptional Modification Human genome has <25,000 genes Yet produces >100,000 different proteins 1 gene codes for an average of 3 different proteins Accomplished by alternative splicing of exons This allows a given gene to produce several different mRNAs 3-39 Post-transcriptional Modifcation non-coding introns removed from mRNA Coding exons spliced together to make the mRNA that will be used in translation multiple splicing patterns for each “pre-mRNA” 1 gene multiple mRNA/proteins 3-38 Alternative Splicing of mRNA: one gene two proteins introns From one gene exons Two types of protein Alternative Splicing of mRNA: one gene 3 proteins From one gene Three types of protein Epigenetics Changes in genetic expression that do not involve changes in base sequences (gene and regulatory DNA has not been altered) Changes in expression are due to changes in histone. Genes can be “turned off” or “allowed to be accessed” Gene silencing (i.e., preventing gene use by making them inaccessible) can be cause by (but is not limited to): Acetylation/deacetylation Methylation/demethylation These changes can be copied and transferred/inherited from generation to generation Can contribute to diseases such as cancer, fragile X syndrome, and lupus Identical twins can have differences in gene expression --because of epigenetic changes in response to differences in their environments 3-74 acetyl, methyl, ubiquitin, phosphate, S.U.M.O DNA (genetics) characteristics/physiology DNA + environment = phenotype (characteristics)