Genomic Organization in Genomic Organization in EukaryotesEukaryotes

Ch 19Ch 19

In Prokaryotes…In Prokaryotes…

• -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…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 PackingDNA 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 First…the Nucleosome “Beads on a StringString

• 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 fiberSecond…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”Third… “Looped Domains”

• Attached to a nonhistone protein scaffold• Coil an fold, further compacting the chromatin

into a mitotic chromosome

Last…the Chromosomal LevelLast…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 KnowWords 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”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 it comes back…the telomere and transposonsand 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 methylationDNA 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: Example of Virus-Oncogene Link: Herpes Virus Seems Linked to Herpes Virus Seems Linked to

Cervical CancerCervical Cancer

Interesting New VaccineInteresting 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 More Linking Virus Genes to Cancer…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.

CarcinogenCarcinogen

Why isn’t cancer more frequent if Why isn’t cancer more frequent if all you need is a proto-oncogene to all you need is a proto-oncogene to

turn into a full blown oncogene?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