Figure 19-01

LE 19-2 DNA double helix Histone tails His- tones Linker DNA (“string”) Nucleosome (“bead”) 10 nm 2 nm Histone H1 Nucleosomes (10 nm fiber) 30 nm Nucleosome 30-nm fiber 300 nm Loops Scaffold Protein scaffold Looped domains (300-nm fiber) Metaphase chromosome 700 nm 1,400 nm

LE 19-3 Signal NUCLEUS DNA RNA Chromatin Gene available for transcription Gene Exon Intro Transcription Primary transcript RNA processing Cap Tail mRNA in nucleus Transport to cytoplasm CYTOPLASM mRNA in cytoplasm Translation Degradation of mRNA Polypeptide Cleavage Chemical modification Transport to cellular destination Degradation of protein Active protein Degraded protein Chromatin modification: DNA unpacking involving histone acetylation and DNA demethylation

LE 19-4 Histone tails Amino acids available for chemical modification DNA double helix Histone tails protrude outward from a nucleosome Acetylation of histone tails promotes loose chromatin structure that permits transcription Unacetylated histones Acetylated histones

LE 19-5 Enhancer (distal control elements) Proximal control elements Upstream DNA Promoter ExonIntron ExonIntron Exon Downstream Transcription Poly-A signal sequence Termination region Intron ExonIntron Exon RNA processing: Cap and tail added; introns excised and exons spliced together Poly-A signal Cleaved 3 end of primary transcript 3 Poly-A tail 3 UTR (untranslated region) 5 UTR (untranslated region) Start codon Stop codon Coding segment Intron RNA 5 Cap mRNA Primary RNA transcript (pre-mRNA) 5 Exon

LE 19-6 Distal control element Activators Enhancer DNA DNA-bending protein TATA box Promoter Gene General transcription factors Group of mediator proteins RNA polymerase II RNA polymerase II RNA synthesis Transcription Initiation complex

LE 19-7 Control elements EnhancerPromoter Albumin gene Crystallin gene Available activators Available activators Albumin gene not expressed Albumin gene expressed Liver cell Lens cell Crystallin gene not expressed Crystallin gene expressed Liver cell nucleus Lens cell nucleus

LE 19-8 Primary RNA transcript DNA or Exons RNA splicing mRNA

LE 19-9 Dicer Hydrogen bond Protein complex miRNA Target mRNA Degradation of mRNA OR Blockage of translation

LE Protein to be degraded Ubiquitinated protein Proteasome Protein entering a proteasome Protein fragments (peptides) Proteasome and ubiquitin to be recycled Ubiquitin

LE Proto-oncogene DNA Translocation or transposition: gene moved to new locus, under new controls New promoter Gene amplification: multiple copies of the gene Point mutation within a control element Oncogene Point mutation within the gene Normal growth-stimulating protein in excess Normal growth-stimulating protein in excess Normal growth-stimulating protein in excess Hyperactive or degradation- resistant protein

LE 19-12_3 Protein overexpressed EFFECTS OF MUTATIONS Protein absent Cell cycle not inhibited Increased cell division Cell cycle overstimulate Effects of mutations Active form of p53 DNA DNA damage in genome UV light Protein kinases MUTATION Defective or missing transcription factor, such as p53, cannot activate transcription Protein kinases (phosphorylation cascade) Cell cycle-inhibiting pathway Cell cycle-stimulating pathway Protein that inhibits the cell cycle NUCLEUS DNA Gene expression Transcription factor (activator) Receptor G protein Growth factor MUTATION Hyperactive Ras protein (product of oncogene) issues signals on its own Protein that stimulates the cell cycle

LE Colon Colon wall Loss of tumor- suppressor gene APC (or other) Normal colon epithelial cells Small benign growth (polyp) Larger benign growth (adenoma) Activation of ras oncogene Loss of tumor- suppressor gene DCC Loss of tumor- suppressor gene p53 Additional mutations Malignant tumor (carcinoma)

LE 19-13a Colon Colon wall Loss of tumor- suppressor gene APC (or other) Normal colon epithelial cells Small benign growth (polyp)

LE 19-13b Larger benign growth (adenoma) Activation of ras oncogene Loss of tumor- suppressor gene DCC Loss of tumor- suppressor gene p53 Additional mutations Malignant tumor (carcinoma) Small benign growth (polyp)

Figure 19-15

LE DNA of genome Transposon is copied Mobile transposon Transposon Insertion New copy of transposon Transposon movement (“copy-and-paste” mechanism) Retrotransposon movement DNA of genome Insertion RNA Reverse transcriptase Retrotransposon New copy of retrotransposon

LE 19-16a DNA of genome Transposon is copied Mobile transposon Transposon Insertion New copy of transposon Transposon movement (“copy-and-paste” mechanism)

LE 19-16b Retrotransposon movement DNA of genome Insertion RNA Reverse transcriptase Retrotransposon New copy of retrotransposon

LE 19-17a DNA Non-transcribed spacer RNA transcripts Transcription unit DNA 18S 5.8S 28S rRNA 18S 5.8S 28S Part of the ribosomal RNA gene family

LE 19-17b Heme Hemoglobin  -Globin  -Globin  -Globin gene family  -Globin gene family Chromosome 11 Chromosome 16    11 11 22      AA Embryo Fetus Adult Fetus and adult The human  -globin and  -globin gene families

LE Duplication of ancestral gene Mutation in both copies Transposition to different chromosomes Further duplications and mutations Ancestral globin gene    11 11 22     AA  -Globin gene family on chromosome 16   -Globin gene family on chromosome 11          Evolutionary time

LE Epidermal growth factor gene with multiple EGF exons (green) EGF FF F F Fibronectin gene with multiple “finger” exons (orange) K K KEGF F Plasminogen gene with a “kringle” exon (blue) Portions of ancestral genes TPA gene as it exists today Exon shuffling Exon shuffling Exon duplication