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Genomic Organization in Eukaryotes Ch 19 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… • -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