Download Genomic Organization in Eukaryotes

Genomic Organization in
Eukaryotes
Ch 19
In Prokaryotes…
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-DNA was circular
-It is smaller that eukaryotic DNA
-Less elaborately structured
-And also, you should know, that it is
loosely anchored by fiber that is anchored
to the plasma membrane (and it’s not in a
nucleus…there is no nucleus!)
But…in eukaryotes…
• -It is complex, with a large amount of
protein to form chromatin
• -Highly extended and tangled in
interphase
• -And then of course for mitosis it gets
short, thick, “fat” and able to be seen
visibly when stained
DNA Packing
• -You need to do it because there is an
enormous amount of DNA
• -There are four levels you will be required
to know. (This is similar to the primary,
secondary, tertiary, and quaternary
structure of a protein in a way…we’re
starting out small and getting to the bigger
picture)
First…the Nucleosome “Beads on
a String
• Histone proteins are associated with this
first level of DNA packing…they have a +
charge to bond with DNA’s – charge
• Nucleosome- DNA wound around a
protein core
• Helps by controlling access of transcription
proteins to DNA
Second…30 nm chromatin fiber
• Structure consists of tightly would coil with
six nucleosomes per turn
• Molecules of histone pulls nucleosomes
into a cylinder 30 nm in diameter
Third… “Looped Domains”
• Attached to a nonhistone protein scaffold
• Coil an fold, further compacting the chromatin
into a mitotic chromosome
Last…the Chromosomal Level
• Chromosomes are extremely condensed DNA +
protein.
• So remember…chromosomes have DNA. DNA
is what makes up genes (sound like an old test
question? )
Words to Know
• Heterochromatin= chromatin that
remains highly condensed during
interphase and is NOT actively transcribed
• Euchromatin= Chromatin that is less
condensed during interphase and is
actively transcribed (it becomes
condensed during mitosis)
• Which of the two would be Barr bodies?
Remember the “Junk”
• Noncoding DNA sequences (“junk DNA”)
account for much of an eukaryote
genome. These are introns.
• In prokaryotes, you “can’t afford this.”
Noncoding DNA sequences actually are
often control sequences…like promoters.
And it comes back…the telomere
and transposons
• Telomere- remember that these are at the
ends of a chromosome? And they are
made by telomerase? Nice to have since
chromosomes shorten slightly after
replication. Well they are an example of
tandem repeats.
• Transposons- “jumping genes” are also
tandem repeats. Often a bad thing…
DNA methylation
• Addition of methyl groups (-CH3) to bases of
DNA…
• Many plants and animals do this, and it seems to
be long-term control of gene expression.
• In eukaryotes, genes that are not expressed (like
Barr bodies) are more heavily methylated
• Methylation ensures that once gene is turned off,
it stays off. (Some problems with drugs that
affect methylation?)
• DNA methylation patterns are inherited…a
chemical record of regulatory events is kept
• In prokaryotes, methylation can be used to
mark its own DNA and keep it separate from
foreign DNA
Words to Know:
• Carcinogens= physical agents such as X-rays
and chemical agents that cause cancer by
mutating DNA
• Oncogene= gene responsible for becoming
cancerous
• Proto-Oncogenes- genes that have potential to
become oncogenes (perhaps by mutation)
• VIRUSES may actually have a role in adding
oncogenes to cells or disrupting DNA
Example of Virus-Oncogene Link:
Herpes Virus Seems Linked to
Cervical Cancer
Interesting New Vaccine
• HPV Vaccine- Approved in June of 2006! This
vaccine is for use in girls/women, ages 9-26
years. The vaccine is given through a series of
three shots over a six-month period. The total
cost is approx. $365.
• The vaccine is a derivative of a surface protein
found in the HPV virus. It launches an immune
response, but because it is only a protein, it
cannot cause HPV itself. It is not 100% effective.
• HPV is the #1 most common STD. In the 1960s,
about 170,000 people visited their doctors with
HPV infections; twenty years later, that number
increased to 1.2 million.
More Linking Virus Genes to
Cancer…
• Hepatitis B virus is linked to liver cancer…
• AIDS virus has been linked to cancer of
the skin…
• and Epstein-Barr virus (the virus that
causes ‘mono’) has been linked to some
cancers of the immune system.
Carcinogen
Why isn’t cancer more frequent if
all you need is a proto-oncogene to
turn into a full blown oncogene?
• It doesn’t seem to be that simple…you
also have tumor suppressor genes on your
side that INHIBIT abnormal cancer growth
• Many cancers (like colon cancer) show a
mutation has occurred in the suppressor
gene as well as the presence of an
oncogene so it has to do a double hit