Einführung in die Genetik - TUM
Transcript of Einführung in die Genetik - TUM
Einführung in die Genetik
Prof. Dr. Kay Schneitz (EBio Pflanzen)http://[email protected]
Prof. Dr. Claus Schwechheimer (PlaSysBiol)http://wzw.tum.de/[email protected]
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Einführung in die Genetik - InhalteEinführung in die Genetik - InhalteEinführung in die Genetik - Inhalte1 Einführung 16. 10. 12 KS2 Struktur von Genen und Chromosomen 23. 10. 12 KS3 Genfunktion 30. 10. 12 KS4 Transmission der DNA während der Zellteilung 06. 11. 12 KS5 Vererbung von Einzelgenveränderungen 13. 11. 12 KS6 Genetische Rekombination (Eukaryonten) 20. 11. 12 KS7 Genetische Rekombination (Bakterien/Viren) 27. 11. 12 KS8 Rekombinante DNA-Technologie 04. 12. 12 CS9 Kartierung/Charakterisierung ganzer Genome 11. 12. 12 CS
10 Genmutationen: Ursache und Reparatur 18. 12. 12 CS11 Veränderungen der Chromosomen 08. 01. 13 CS12 Genetische Analyse biologischer Prozesse 15. 01. 13 CS13 Transposons bei Eukaryonten 22. 01. 13 CS14 Regulation der Genexpression 29. 01. 13 KS15 Regulation der Zellzahl - Onkogene 05. 02. 13 CS
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Regulation of Gene Expression
Genetics 14
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Summary• Cells respond to intrinsic and extrinsic signals by modulating
transcriptional control of certain genes
• Gene activity is the result of the function of cis- and trans-acting factors
• Trans-acting proteins react to environmental signals by using built-in sensors that continually monitor cellular conditions
• Coordinated gene regulation in bacteria
• genes are often clustered into operons on the chromosome and transcribed together as multigenic mRNAs
• one cluster of regulatory sites per operon is sufficient to regulate expression of several genes
• Negative vs positive regulation
• repressor proteins bind to DNA at operator site thereby blocking transcription (e.g., lac operon)
• activator proteins activate transcription by binding to DNA at the promoter region (e.g., cAMP/CAP regulation of lac operon)
• Molecular anatomy of genetic switch
• regulatory proteins have DNA-binding domains (e.g., HLH) and protein-protein interaction domains (modular
• specificity of gene regulation depends on specific protein-DNA interactions mediated by the chemical interactions between aa side chains and chemical groups of DNA bases
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Summary• Eukaryotic gene regulation resembles bacterial gene regulation
• trans-acting factors binding to cis-regulatory elements on the DNA
• this regulatory factors determine the level of transcription by regulating the binding of RNA pol II to the promoter of a gene
• Enhancers/UAS
• cis-regulatory elements, possibly located quite far away (>10-50kb) from promoter
• combinatorial interactions among different transcription factors
• enhanceosome: complexes of regulatory proteins that interact in cooperative and synergistic fashion --> high levels of transcription through recruitment of RNA pol II
• Gene regulation and chromatin
• eukaryotic genes are packed in chromatin
• activation/repression requires specific modifications to chromatin
• genes are mostly turned off and kept silent in part by nucleosomes and condensed chromatin
• histone code: pattern of posttranslational modifications of histone tails (acetylation, methylation, phosphorylation etc).
• histone code is an epigenetic mark involved in nucleosome positioning and chromatin condensation that can be altered by TFs
• TFs recruit for example ATP-dependent chromatin remodelers (e.g., SWI-SNF)
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Control of cell number - oncogenes
Genetics 15
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Tumors
The cell cycle
Apoptosis
Cancerogenesis
The ubiquitin-proteasome system
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Tumors
malignant vs. benign tumors
uncontrolled cell divisions and growth
invasion and colonization of tissue
metastasis
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Tumor types
carcinoma - epithelial cell cancer
sarcoma - connective tissue or muscle cancer
leukemia or lymphoma - blood cell cancers
others
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Tumors - incidence rates
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Tumors - types and distribution
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The cell cycle
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FACS sorting (fluorescence activated cell sorting)
Cell cycle studies
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Cell cycle studiesNorthern blot
Western blot
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Cell cycle mutants of yeast
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Temperature sensitive mutants in cell cycle analysis
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Major check points in cell cycle control
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Cell cycle studiesNorthern blot
Western blot
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Cyclins and cyclin-dependent kinases are differentially transcribed throughout the cell cycle
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Cyclins and cyclin-dependent kinases (CDKs)
Cyclin-CDK ! Vertebrates ! ! Yeast!Complex !Cyclin ! Cdk ! !Cyclin ! Cdk!
G1-Cdk ! !Cyclin D Cdk4, Cdk6 !Cln3 ! Cdk1!G1/S-Cdk !Cyclin E! Cdk2 ! !Cln1,2 ! Cdk1!S-Cdk ! !Cyclin A ! Cdk2 ! !Clb5,6 ! Cdk1!M-Cdk ! !Cyclin B! Cdk1 ! !Clb1,2,3,4 Cdk1!
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Cyclin-CDK complexes control the cell cycle
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Mitosis promoting factor and cyclins
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Cell cycle control by Cyclin-CDKs
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Cell cycle control by Cyclin-CDKs
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Cyclins and CDKs in cell cycle control
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Mitotic cyclins and protein phosphorylation
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The ubiquitin-proteasome systemand protein degradation
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The ubiquitination machinery
E1 ubiquitin activating emzyme
E2 ubiquitin conjugating emzyme
E3 ubiquitin ligase
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The ubiquitination machinery
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The 26S proteasome
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Mitotic cyclins and protein degradation
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The anaphase promoting complex (APC)
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Cancerogenesis
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Major check points in cell cycle control
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Examples for receptors in signaling
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Receptor tyrosine kinases
JAK/STAT pathwayThursday, January 31, 13
Receptor tyrosine kinases
Growth factors (EGF, TGF etc.)
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Ras
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Ras
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The Retinoblastoma (RB) tumor suppressor
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Retinoblastoma protein (Rb) blocks E2F
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Prelavance of p53 tumour-suppressor mutations
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p53 is phosphorylated in responseto DNA damage
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p53 phosphorylation blocks the cell cycle
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p53 phosphorylation blocks the cell cycle
p53 +/+
daysThursday, January 31, 13
Mutations can induce cancer
RasRb
p53
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Summary• Tumours are the result of uncontrolled
and invasive cell divisions and cell growth
• The cell cycle is governed by cyclins and cyclin-dependent kinases
• Cyclins and cyclin-dependent kinases are under transcriptional control
• Cyclins are degraded by the UPS
• E1, E2, E2 enzymes and ubiquitin
• 26S proteasome
• Apoptosis regulated cell number
• Apoptosis is a controlled process
• p53, RB and Ras are important cell cycle regulators
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The end
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