Homework #2 is posted and due 10/17 Exam key is posted
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•Homework #2 is posted and due 10/17
•Exam key is posted
Altering DNA’s Shape can Alter Gene Expression
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How is class going?
1. The speed of lecture is:1= too slow – 5= too fast
2. After lecture I understand the material:1= barely – 5= very well
3. Class is enjoyable/interesting:1= no – 5= yes
4. The grade that I think I earned on exam 1=0–100
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• Overview of transcriptional regulation
Figure 11-2
Fig 11.2
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Mutations in the promoter show critical nucleotides
Fig 11.4
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Fig 16.1
Gene Expression is controlled at all of these steps:•DNA packaging•Transcription•RNA processing and transport•RNA degradation•Translation•Post-translational
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Different levels of DNA packaging Fig 11.10
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Tightly packaged DNA is unavailable. DNA packaging changes as the need for different genes changes.
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Fig 11.12
Histones can be post-translationally modified, which affects their abililty to bind DNA.
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Acetylation (-COCH3): post-translational modifications of the histones loosen DNA binding
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Acetylation of histones (-COCH3) causes a loosening of the DNA/histone bond…unpackaging the DNA.
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Four-stranded DNA: cancer, gene regulation and drug developmentby Julian Leon HuppertPhilosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering SciencesTriennial Issue of 'Chemistry and Engineering’DOI: 10.1098/rsta.2007.0011Published: September 13, 2007
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4 strand DNA Fig 1
Four-stranded DNA forms between sequences of guanines…G-quadruplexes
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4 strand DNA Fig 1
Four-stranded DNA forms between sequences of guanines…G-quadruplexes
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4 strand DNA Fig 2
The G-quadruplexes can form from 4, 2, or 1 DNA strand.
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Fig 7.11
During DNA replication, the ends of the DNA are not completely copied.
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Telomeres are non-gene DNA at the ends of DNA strands.
Telomeres are shortened during DNA replication.
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Fig 7.26
Telomeres can be lengthened by telomerase.
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The telomeric cap structure is one place where G-quadruplexes can be found
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Telomeres are non-gene DNA at the ends of DNA strands.
Short telomeres will cause cells to stop replicating or cell death.
The critical size is unknown.
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Drugs that can block the action of telomerase, by binding the G-quadruplexes, are being
investigated to treat cancer.
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Fig 11.3
Eukaryotic promoters often contain G-rich areas
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4 strand DNA Fig 5
G-quadruplex in promoters
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If the promoter is defined as 1 kbase upstream of the transcription start site:•Quadruplex motifs are significantly overrepresented relative to the rest of the genome, by almost an order of magnitude.
•almost half of all known genes have a putative quadruplex-forming motif
•By comparison, the TATA box motif—probably the best-known regulatory motif and a staple of undergraduate textbooks—is found in only approximately 10% of genes.Four-stranded DNA: cancer, gene regulation and drug development by Julian Leon Huppert in Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences Triennial Issue of 'Chemistry and Engineering’ DOI: 10.1098/rsta.2007.0011 Published: September 13, 2007
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Four-stranded DNA: cancer, gene regulation and drug development by Julian Leon Huppert in Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences Triennial Issue of 'Chemistry and Engineering’ DOI: 10.1098/rsta.2007.0011 Published: September 13, 2007
Oncogenes, the genes involved in cancer, are especially rich in potentially regulatory quadruplexes—69% of them have such motifs
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Werner syndrome, which causes premature aging, is caused by the lack of a helicase that binds to G-quadruplexes.
Four-stranded DNA: cancer, gene regulation and drug development by Julian Leon Huppert in Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences Triennial Issue of 'Chemistry and Engineering’ DOI: 10.1098/rsta.2007.0011 Published: September 13, 2007
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G-quadruplex ligands
G-quadruplex
BRACO-19
TMPyP4
telomestatin
4 strandDNAFig 6
Down regulates telomerase and some oncogene transcription
Specifically binds to telomeres, naturally occurring in Streptomyces anulatus
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4 strand DNA Fig 7
Model of specific G-quadruplex ligand binding to G-quadruplex and a specific DNA sequence
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•Homework #2 is posted and due 10/17
•Exam key is posted
Altering DNA’s Shape can Alter Gene Expression