Download 10/3

Altering DNA’s Shape can Alter
Gene Expression
•Homework #2 is posted
and due 10/17
•Exam key is posted
How is class going?
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2. After lecture I understand the material:
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3. Class is enjoyable/interesting:
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• Overview of transcriptional regulation
Figure 11-2
Fig 11.2
Mutations in the promoter show critical
nucleotides
Fig 11.4
Gene Expression is controlled
at all of these steps:
•DNA packaging
•Transcription
•RNA processing and
transport
•RNA degradation
•Translation
•Post-translational
Fig 16.1
Different levels of DNA packaging
Fig 11.10
Tightly packaged DNA is unavailable. DNA
packaging changes as the need for different
genes changes.
Histones can be posttranslationally
modified, which
affects their abililty
to bind DNA.
Fig 11.12
Acetylation (-COCH3):
post-translational
modifications of the
histones loosen DNA
binding
Acetylation of histones
(-COCH3) causes a
loosening of the
DNA/histone
bond…unpackaging the
DNA.
Four-stranded DNA: cancer, gene regulation
and drug development
by Julian Leon Huppert
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
Four-stranded DNA forms between sequences
of guanines…G-quadruplexes
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
4 strand DNA Fig 1
Four-stranded DNA forms between sequences
of guanines…G-quadruplexes
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
4 strand DNA Fig 1
The Gquadruplexes
can form from
4, 2, or 1 DNA
strand.
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
4 strand DNA Fig 2
During DNA replication, the
ends of the DNA are not
completely copied.
Fig 7.11
Telomeres are non-gene DNA at the
ends of DNA strands.
Telomeres are shortened during DNA
replication.
Telomeres can be
lengthened by
telomerase.
Fig 7.26
The telomeric cap structure is one place where
G-quadruplexes can be found
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.
Drugs that can block the action of telomerase,
by binding the G-quadruplexes, are being
investigated to treat cancer.
Eukaryotic promoters often contain G-rich
areas
Fig 11.3
G-quadruplex in promoters
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
4 strand DNA Fig 5
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
Oncogenes, the genes involved in cancer, are
especially rich in potentially regulatory
quadruplexes—69% of them have such motifs
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
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
G-quadruplex ligands
TMPyP4
BRACO-19
Down regulates telomerase and
some oncogene transcription
G-quadruplex
telomestatin
Specifically binds to telomeres, naturally
occurring in Streptomyces anulatus
4 strand
DNA
Fig 6
Model of specific G-quadruplex ligand binding
to G-quadruplex and a specific DNA sequence
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
4 strand DNA Fig 7
Altering DNA’s Shape can Alter
Gene Expression
•Homework #2 is posted
and due 10/17
•Exam key is posted