UNT BIOL 3451 - Regulation of Gene Expression in Eukaryotes and Cancer (5 pages)

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Regulation of Gene Expression in Eukaryotes and Cancer



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Regulation of Gene Expression in Eukaryotes and Cancer

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Finish up gene regulation in eukaryotes and begin discussing cancer and cell cycle regulation. Begin discussing cancer and how it is regulated.


Lecture number:
23
Pages:
5
Type:
Lecture Note
School:
University of North Texas
Course:
Biol 3451 - Genetics
Edition:
1
Documents in this Packet
Unformatted text preview:

BIOL 3451 1st Edition Lecture 23 Outline of Last Lecture I 17 2 Programmed DNA Rearrangements Regulate Expression of a Small Number of Genes II 17 3 Eukaryotic Gene Expression Is Influenced by Chromatin Modifications III 17 4 Eukaryotic Transcription Initiation Is Regulated at Specific Cis Acting Sites IV 17 5 Eukaryotic Transcription Initiation Is Regulated by Transcription Factors That Bind to Cis Acting Sites V 17 6 Activators and Repressors Interact with General Transcription Factors at the Promoter VI 17 7 Gene Regulation in a Model Organism Transcription of the GAL genes of Yeast Outline of Current Lecture I 17 7 Gene Regulation in a Model Organism Transcription of the GAL genes of Yeast II 17 8 Posttranscriptional Gene Regulation Occurs at All the Steps from RNA Processing to Protein Modification III 17 9 RNA Silencing Controls Gene Expression in Several Ways IV 19 1 Cancer is a Genetic Disease That Arises at the Level of Somatic Cells V 19 2 Cancer Cells Contain Genetic Defects Affecting Genomic Stability DNA Repair and Chromatin Modifications Current Lecture I 17 7 Gene Regulation in a Model Organism Transcription of the GAL genes of Yeast o GAL1 and GAL10 controlled by central control region UASG UAS are functionally similar to enhancers in eukaryotes Four binding sites for Gal4 protein regulator Fig 17 11 Chromatin structure of UAS is constitutively open or DNase hypersensitive meaning that it is free of nucleosomes o Mutation in the regulator of GAL4 prevents activation Thus Gal80p is positive regulator controls transcription this way 1 Regulator must be present to turn on gene transcription II 17 8 Posttranscriptional Gene Regulation Occurs at All the Steps from RNA Processing to Protein Modification o Transcriptional control major type of regulation in eukaryotes posttranscriptional regulation plays just as much of a role or more These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute III Includes 1 Removal of introns and splicing together of exons 2 Addition of a cap and poly A tail 3 Translation 4 Stability o Alternative splicing generate different forms of mRNA from identical pre mRNA gives rise to a number of proteins from one gene splice exon as in intron to change protein functions as a result number of proteins that a cell can make its proteome is not directly related to number of genes in genome our bodies make like a million different proteins but down to about 25 000 genes how possible alternative splicing we think about 2 3 of genes do alternative splicing allows humans to produce several hundred thousand different proteins from like 25 000 genes mutations in some diseases affect regulation of splicing spliceopathies 1 fragile X Huntington myotonic dystrophy 2 fig 17 13 a four is skipped stop codon there bc became intron 1 2 3 5 6 b can get functionally similar results or something quite different o Sex lethal Sxl transformer tra doublesex dsx genes are part of a hierarchy of gene regulation for sex determination in Drosophila Fig 17 15 signaling cascade results in male or female o Steady state level amount of mRNA in a cell determined by combination of transcription rate and rate of mRNA degradation Determines amount of mRNA available for translation and regulated in response to cellular needs Can be regulated in many ways 1 Degradation done by higher eukaryotes best way found so far to do this 2 Translational level blocking using repressors 3 Posttranslational stability of protein can be modulate a P53 protein b Can change structure and hence activity 17 9 RNA Silencing Controls Gene Expression in Several Ways o RNA silencing can be used Not done a lot in humans but in plants yes Short RNA molecules regulate gene expression by triggering mRNA degradation and repressing translation 1 Posttranscriptional regulation known as RNA interference RNAi 2 Together these phenomena known as RNA induced gene silencing IV o RNAi uses protein DICER to cut up double stranded mRNA into small interfering RNAs siRNAs and micro RNAs miRNAs Repress MRNA translation and trigger degradation Bind to mRNA through DICER when base pairs means I should kill you Inhibit transcription of specific genes by associating with RNA induced initiation of transcription RITS and RNA induced silencing complex RISC complex Fig 17 16 o RNAi technology big in lab and now looking at pharmaceutical agent Study diseases caused by overexpression of specific gene or normal expression of abnormal gene product use RNAi to as therapeutic product Results in reducing severity of HIV and influenza polio Animal models 1 Viral infection 2 Eye diseases 3 Cancer 4 Inflammatory bowel disease RNAi holds powerful promise for molecular medicine 19 1 Cancer is a Genetic Disease That Arises at the Level of Somatic Cells o Genetic disease at the somatic level resulting from mutated gene products or abnormally expressed genes Can inherit vulnerabilities but most often done to ourselves Two fundamental properties 1 Unregulated cell proliferation 2 Metastatic spread usually what kills you o Mutations Single nucleotide substitutions Large scale chromosomal rearrangements Amplifications quantity not quality issue Deletions Usually there are multiple nucleotide changes Fig 19 1 o Most cancers are somatic the inherited risk for cancer is large 1 due to germline mutations Rarely arises from gene mutations but usually from accumulation of mutations in many genes 6 12 These affect DNA repair usually results in different kinds of cancer cell division very common apoptosis cellular differentiation migratory behavior and cell cell contact metastatic Fig 19 1 lots of aneuploidy 1 Lots of translocation different colors on chromosomes V Benign tumors don t move and probably won t kill you unless in a really bad spot most cases easily removable by surgery can be deadly if not removed depending on area Malignant tumors when begins to spread by metastasis invading other tissue becomes life threatening o All cancer cells in primary and secondary tumors are clonal means that they originate from one cell that accumulated numerous specific mutations Reciprocal translocations are characteristic of many cancers o Burkitt s lymphoma shows reciprocal translocations between chromosome 8 and chromosomes 2 14 or 22 Onco gene present divide divide divide o X chromosome inactivation occurs early in development and occurs at random all cancer cells


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