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Class of Molecular and Cellular Biology
Academic Year Class of Molecular and Cellular Biology
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Struttura e funzioni di acidi nucleici e proteine
attraverso l’analisi di meccanismi molecolari fondamentali in Procarioti ed Eucarioti
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Prokaryotes and Eukaryotes
Archea Bacteria Prokaryotes
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1 mm 5 mm
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GENOMI
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Genomes of Prokaryotes
E. coli 4.6 x 106 base pairs “Compact” genome Polycistronic mRNAs
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Human genome 46 chromosomes 22 autosomes in double copy (diploid genome) 2 sexual chromosomes X Y male; X X female 3,6 x 109 base pairs (aploid genome) HUMAN KARYOTYPE
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A PATHOLOGIC HUMAN KARYOTYPE
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GENOME COMPLEXITY Escherichia coli 4,6 x 106 base pairs
~ 4 x 103 genes 103 Homo sapiens 3,6 x 109 base pairs ~ 3 x 104 genes 101
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GENOME ANNOTATIONS
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> 10 x GENOME ~ 3 x 104 genes TRANSCRIPTOME (alternative splicing)
PROTEOME (post-translation modifications) 105÷106 products
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Post-Genomics: Analysis of Transcriptomes and Proteomes
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Molecular mechanisms of diseases…
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…and identification/optimization of therapeutical targets
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Genome: structure and maintenance
The genome Chromatin DNA Replication DNA damage and repair Recombination Genome activities Transcript synthesis and processing Protein synthesis Gene expression regulation
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-> nucleus <- cytosol
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Figure 4-21 Molecular Biology of the Cell (© Garland Science 2008)
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CHROMATIN STRUCTURE
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NUCLEOSOMES
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HISTONES
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Figure 4-25 Molecular Biology of the Cell (© Garland Science 2008)
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NUCLEOSOME ASSEMBLY Figure Molecular Biology of the Cell (© Garland Science 2008)
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Figure 4-27 Molecular Biology of the Cell (© Garland Science 2008)
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Figure 4-31 Molecular Biology of the Cell (© Garland Science 2008)
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Figure 4-33a Molecular Biology of the Cell (© Garland Science 2008)
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Figure 4-33b Molecular Biology of the Cell (© Garland Science 2008)
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Figure 4-34 Molecular Biology of the Cell (© Garland Science 2008)
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Genetics ed Epigenetics
Figure Molecular Biology of the Cell (© Garland Science 2008)
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HISTONE MODIFICATIONS
Figure Molecular Biology of the Cell (© Garland Science 2008)
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Histone code Figure 4-44a Molecular Biology of the Cell (© Garland Science 2008)
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Figure 4-39b Molecular Biology of the Cell (© Garland Science 2008)
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Figure 4-72 Molecular Biology of the Cell (© Garland Science 2008)
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EU- and HETERO-CHROMATIN
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DNA TOPOLOGY AND CHROMATIN COMPACTION
Prokaryotes Eukaryotes
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Denaturation and Supercoiling
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DNA IN MESOPHILES IS NEGATIVELY SUPERCOILED WHAT ABOUT TERMOPHILES ?
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Topoisomerase I
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TOPOISOMERASE I: Mechanism
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Topoisomerase II
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Topoisomerase II: Mechanism
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Topoisomerasi I inhibitors: Topotecan (der. Camptotecine)
Staker et al. (2002) PNAS 99,15387 Topoisomerase II inhibitors: Etoposide, doxorubicine, daunorubicine, mitoxantrone
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Etoposide Topo II poisons that include many clinically useful anticancer drugs, such as doxorubicin, daunorubicin, mitoxantrone and m-AMSA in addition to etoposide, stabilize the cleavable complex.
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