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DNA Condensed Notes. Timeline • • • • • • • • • • • 1865- Mendel- traits are passed as distince alleles (various forms fo the same trait) • ex: trait= eye color • alleles= blue, green, hazel, brown • Mendel studdied patterns of train inheritance- nothing about the mechanisms and chemicals invovled. Not many people read his paper. 1869- Friedrich Miescher discovered deoxyribonucleic acid. naming nuclein --> nuclei acid-=> deoxyribonucleic acid. 1900- deVries, Correns, Tschermak independently rediscover Mendel's work. • what a coincidence! none of them have heard of Mendel before. all three wrote their papers within three weeks of each other. all of them turned them in to nature magazine to be published at the same time 1908- Hardy and Weinbertg- laws of population genetics determined a math formula that explains how recessive traits stay constant in a stable population. • fathers of population genetics. 1910- Morgan- "genes" are on chromosomes. thread things had been seen in cells doing the mitosis thing. Morgan determined that they contained the trait passing capcity. coined the term "gene" 1928- Griffith- first transformation experiments DNA could be the genetic stuff. 1941- Beadle and Tatum: " one gene codes for one polypeptide" hypothesis. Polypeptidechain of amino acids, the fundamental building blocks of proteins. 1944- Avery, Colin McLeod, McCarty team, proved that dna is the genetic stuff. 1950- Chargraff's Rules • T=A • C=G 1952- Hershey and Chase- second team to prove that dna is the genetic stuff. 1953- Watson, Crick, Wilkins and Franklindetermined that dna is a double helix. Published in NATURE. Won the Nobel Prize Page 1 of 6 • • 1962 (except for Franklin- she died). 1958- Meselson and Stahl- proved that DNA replicates semi conservatively. 1966- Nirenberg and Khorana: break the genetic language code. MACROMOLECULE 4, NUCLEIC ACIDS micromolecule: nucleotides all nucleotides are made of three parts: • phospate group • five carbon sugar, pentose • a nitrogen contining base 1. Phosphate group has negative charge. if you add an H you get phosphoric acid. 2. five carbon sugar- pentose 2 possibilties, know the numbering of carbons. ribose: has OH on the two carbon. Used in RNA. deoxyribise: no OH on the scond carbon, used in DNA. 3. Nitrogen containing Bases 5 different types (see picture pages) DNA/RNA T/U G/G C/C A/A some are single rings: pyrimidines some are double rings: purines purines: adenine, DNA RNA. guanine DNA and RNA. "puga" pyrimidines: thymine RNA only, ctosine DNA and RNA, uracil RNA only. "if you sit naked on top of a pyrimid it will C.U.T. you!" Two dehydration synthesis reactions: phosphate: joins to the number five carbon of sugar base: joins to the number one carbon of sugar. A base and a sugar is known as a nucleoside: ex: adenine and ribose=adenosine Other important nucleotides.. DNA Condensed Notes. 1. ATP (adenosine tri-phosphate) 3 phosphates--ribose sugar--adenine base. The most important of all nucleotides it is the nergy transfer molecule. gold of the cel, energy currency, high energy bonds. fully charged-->partially charges---> run down. Page 2 of 6 other only has one ring. These pile designations are important. purines: those that are double ringed. (drink two glasses of urine a day for good health.) pyrimidines: those that have only one ring. (All built one pience at a time, no double room pyramids, etch.) see picture pages: know how ATP works, recharged in mtchondria like a NiCad battery. PUGA: purines: guanine and adanine. if you sit naked on pyramids, it iwll cut you thymine, cytosine, uracil. Mitocchondria is a battery rechargeer--putst he Fi back on. The five bases are: adenine, guanine, thymine, cytosine, uracil. 2. NADP+ a coenzyme used in photosynthses 3. FAD+ a coenzyme used in cellular respiration. how to build a nucleotide you have to have a pentose (deoxyribose or ribose), the phosphate group, and the bases. 12/9/02 1:06 pm DNA and DNA ase made up f nuclaic aids ribonuclaic acid deoxyribonuclaic acid. every nucleotide is made up of a phosphate group (a derivitive of phoshphoric acid), the phosphate groups are negatively charged. They hydrogens donated by DNA and RNA come from the phosphate groups. The phosphate groups are identical in the both. Nucleotides: made up of phosphate groups,pentose sugar, nitrogen containing base. the two different pentoses are ribose and deoxyribose, respectively. In dna you use: guanine and adanine. and tymine and cytosine. If you see a uracil it is a mutation and it will be removed, you will never find it tere. In your rna you have Guanine and adanine, and cytosine and uracil. There is no tymine in RNA. Uracil and thymine trade places. Within a single nucleotide: the base is always hooked to the one primary carbon and the phsophate is always hooked on to the five primary carbon. This will always happen. To construct the nucleotide togeterh you will have to do a condensation reaction (times two). Phosphates are always represented by a circle, sometimes with a P in it. It is imperitive for todays lecture that you learn the numberingb for ribose and deoxyriose. Starting form tghe oxygen, you number them clockwise around the ring, witt he fifth carbon sticking out of the ring. Now when you link nucleotides together it's a polyumerization reaction. The phophate of one nucleotide attaches to the three prime carbon of the sugar in nuclotide above. (number of linked-1) Phosphate goins five prime carbon if it's own nucleotide. The difference between ribose and doxyribose moleculary is that the deoxyriose has been deoxygenized, it is missing a hydroxyl group. "Deoxyribose is missing a hydroxyl group off of the two primary carbon." The differnece between one side of the dna and the other is that on one side the dna has the oxygens pointing up, while on the other side the oxygens are pointing down. Everything in dna and rna are described in the terms of the numbering system of the sugar. You must know this. The prime is after them because they are that important. You must learn what the prime designations are (the aprostaphe ' thing). The last part of the nucleotides are the bases. The basic shape difference is that one pile has two rings, while the If you look at the dna like a ladder, there will always be a phosphate group attached to it's own five carbon sugar in a corner, it is then called the five prime corner. It is the top left of hte ladder. The oxygens point up on that vertical column. The bottom left corner are the three prime corner. Opposite the three prime corner on the other side, since it is reversed, is the five prime corner, you then have the three prime on the top right of the ladder. The right and left side of the dna are built upsidedown to DNA Condensed Notes. Page 3 of 6 each other. It's called antiparallel construction. (like shoes in a shoebox). Shape is a double helix (a twisted ladder). Watson, Rick, Wilkins, and Franklin determined the shape in 1954. The steps of a ladder are referred to as the rungs of a ladder. The steps of a ladder are the nitrogen containing bases. The side rails of the ladder are the alternating phosphates and sugars. Side rails of ladder: P-S-R-S-P-S-P-S TA, CG. a purine and a pyrimidine are always matched up on a single step, maintaing the 2 nm constant width of the dna. the standard width would be around three rings wide. .34 nanometers is the distance between the centers of each step. The bonds between nucleotides are called phosphodiester bonds. The middle of each step are held together by hydrogen bonds, not actual covalent bonds. this is so you can unzip the dna during mytosis. Every other bond in the dna is a covalent bond. phosphodiester bonds: COPOC. From theh three carbon, to the oxygen, to the phosphorus, to the oxygen, to the five prime carbon. The two nucleotides that make up one secition (step and siderails) are called a base pair. They are held together by the hydrogen bond. If you go though and add up the weight of all the atoms, thus the base pair is 660 daltons (amu's). The average gene is 1200 base pairs long. 12/10/02 1:20 pm Each step (rungs) of the ladder= two bases side by side. T with A: 2 H bonds G with C: bound by 3 H bonds Average gene is 1200 base pairs long. Puring always hydrogens to a pyrimidine. Rungs of ladder are always three rings wide. wide and narrow groves. complementary, fit togetherbut are not identical. RNA: looks like half of a dna ladder a cob messenger from dna to the ribosmes. T bas is never used Looks like a ladder buzz sawed down the middle. Always use the pentose ribose in its nucleotides. 12/11/02 1:04 pm 12/16/02 1:10 pm Donner Party they left too late and got stuck in the Sierra Nevada mountains. They got stuck in a snowstorm and had to spend the winter. 5 billin nucleotide in one human genome 2 chaines of nucleotides, side by side, hydrogen bonded together at the bases. 3/21/03 11:28 am messleson and stahl: semiconservative replication. • • • • • • • bluerint molecule of life complete set of instructions for you. complete set in every cell of your body directs wthich proteins will be made in the cell on a daily basis the enetic material that directs what your babies will be lilke always in the nuclus, never ever leaves. The guard proteins keep it in there at all costs. always uses the pentose deoxyribose in it's nucleotides. **One gene codes for one polypeptide chain. The ribosomes will then go out and make that polypeptide chain as specified. DNA REPLICATION DNA replication takes place during the S (synthesis) part of the cell cycle. 1. Helicase: opens hydrogen bonds of DNA ladder to form a replicating bubble at the origin of replication. Spends two ATP/per bond to open. breaks the double helix, pulls apart the hydrogen bonds. often end up with two forks, (replication forks). the place where helicase started is the origin of replication. the entire open area is the replication bubble. Spends two atp per bond to open. 2. There is one replicating bubble in prokaryotesmultiple replicating bubbles in Eukaryotes. you have DNA Condensed Notes. many origins of replication, sequences with lots of T and A. 3. Eukaryotes build new complimentary DNA- 50 nucleotides/second. 4. Prokaryotes build new complimentary DNA500 nucleotides /second. Why the difference in rates??? they do it alot faster than eukaryotes. they are much faster because they don't' live as long as eukaryotic cells and because prokaryotic cells do not have as many error checking mechanisms as eukaryotes. One out of every ten million base pairs in eukaryotes is incorrect. in prokaryotes it is one ouut of every thousand/ten thousand. 5. Like kite string being pulled apart in the middle of a strand, DNA would bend and kink while being unwound if the topoisomerase did not work ahead (upstream) of the helicase relieving the stress. prevents the tension of the dna molecule by allowing it to spin. 6. Movement is bi-directional the bubble grows in both directions. 7. the points on the ladder where the hydrogen bonds between the bases are being opened are called Replicating forks. 8. DNA nucleotides must join on to a 3' OH above it. First nucleotide has a problem. there is not 3'OH to join on to. DNA strands must always build 5' to 3'. 9. So… RNA nucleotides must be put in place first to supply the 3' OH for the DNA nucleotides to hook onto Look at your detail picture. About 10-12 RNA nucleotides start the new strand. these are called an RNA Primer. The RNA nucleotides cannot stay there forever and must later be cut out and replaced with DNA nucleotides. 10. RNA primase is the enzyme which places the RNA primer in position. 11. excisions endonuclease "cuts" out the RNA nucleotides and 12. DNA Polymerase puts the correct DNA nucleotides in place and... 13. DNA Ligase will "patch" the strand back together (fixes phosphodiester bonds!) the Elmer's glue of enzymes. 14. One new side is easy to build. ONe RNA primer and then the process continues to build 5'-3'. The strand is called the leading strand. easy side: leading strand hard strand: lagging strand Page 4 of 6 15. The other side is tougher. It must keep putting in RNA primers as the helix opens up and makes sites available. The primers must keep being removed and DNA patched in to fill the spaces. This is called the Lagging Strand. the short little segments of DNA that can be fabricated and eventually patched together are called Okazaki Fragments. 16. The Okazaki fragments in prokaryotes are typically 1000-2000 nucleotides long. In eukaryotes they are 100-200 nucleotides long. 17. Additional point. As the DNA helix is opened by the helicase enzyme, it would quickly close back up before the new complimentary nucleotides could be placed if they weren't held open. Single Stranded Binding Proteins do this job. 18. Proofreading: DNA polymerasae also checks to be sure the correct nucleotide was placed in the growing chain. It is the number one proofreading enzyme in DNA replication. 19. The new DNA nucleotides that are going to be placed in the growing strand float in as tri-phosphate nucleotides. The extra two phosphates (P~P) are removed by DNA polymerase and supply the energy for their condensation into the strand. DNA Replication in Prokaryotes Special Points As you know, bacteria usually replicate by binary fission. • The ring of DNA is attached at one point to the cell membrane. • An origin of replicating starts opening up into a replicating bubble and the ring is duplicated as described above. • This method is called "theta" replication because it kinda looks like the Greek letter theta while it is happening. News Flash!!! Bacteria sometimes have sex! It's called conjugation. and that long ting between them is called a pilus. The shorter spikes are usually called fimbrae. there is a certain gene that allows the bacteria to make the spikes.. the long one is the pilus, the short ones are fimbrae. the bacteria that can give bacteria are the males. Other news: besides the regular ring chromosome of DNA in a bacteria, they usually ahve smaller circles of extra DNA called plasmids. DNA Condensed Notes. Plasmids• carry anywhere from 2 to 10 genes on them. • a rare few have been found with thirty genes in them. • cells can have anywhere from a couple to fifty or more plasmids in them. • some pop into the bacterial chromosome = episomes. Page 5 of 6 Drug resistance is also passed from bacteria to bacteria this way. Serious medical implications. concatemer: a piece of the replicated dna that is one entire revolution (genome). plasmids end up getting alto of genes that are on the genome. they jump in and out as episomes. there is alot of genetic variation. when the bacteria replicates the plasmids sometimes replicate as well. because plasmids are sent over so easily it is easy to have antibiotic resistance. • The dna comes out like a two ply sheet of toilet paper as opposed to a replication bubble. • • some plasmids only replicate when the ring chromosome replicates. Other plasmids replicate on their own schedule. Important genes they might carry: Drug resistance fertility factor (F+) if you have f+, you are a male, if you are F-, you are a female. during conjugation plasmids can be transferred from one bacteria to another. F+ has gene to make a pilus. helicase starts at the point of origin! single stranded binding proteins keep the helix from reforming. they actually cover over the half strand and thus cover where the hydrogen bonds would be and it keeps the strand from re helixing. the primer is about ten to twelve units in length! 3/31/03 11:52 am How to fold a strip of DNA into a chromosome Before mitosis and meiosis, all the linear strips of DNA in the cell must fold up into the chromosomes. During most of the cell cycle, DNA is loose and unwound so the bases can be reacehd. Tangled mess if you tried to separate them like that during mitosis. Two meters of DNA in each human cell. The folding process is called condensation. it takes about ten to twelve nucleotides to cause the electrostatic interactions to cause rna primase to fall away from the chain. Histone protein spools are the key component around which the DNA wraps itself. Histones have large amounts of positively charged amino acids (lysine and arginine). bacteria are not conservative with their genes. 1/2 of the weight of a chromosome is protein. 3/26/03 12:58 pm During the interphase, much of the DNA stays wound up partially with these proteins. If a bacteria has fertility factor (F+), it has the genes for growing a pilus. (And is known as the male partner). When bacteria conjugate, they do not use theta replication Instead, they use the rolling circle method. This allows multiple copies of the chromosome or plasmid to be made at once in one long strip an then injected through the pilus to the mating cell. Fast quick method of dispersing resistance. Histones come in five flavors: • H1 • H2a • H2b • H3 • H4 3/31/03 11:35 am If an F- cell (female partner) receives the fertility factor plasmid from conjugation it then becomes a F+ cell. Sobering thought: maleness is contagious A histone core (histone spool) is made up of eight of these proteins: • H2a H2a • H2b H2b • H3 H3 • H4 H4 DNA Condensed Notes. it looks like a double layered cheese cake cut into four pieces. each layer is exactly the same. each one of the four pieces is one of the histone proteins. The H1 proteins are not in the histone core. Histone genes are highly conserved sequences in all eukaryotes. ex: H4 from cow varies from the H4 for peas by only 2/102 amino acids. Page 6 of 6 tortoise-shell cat (calico) males extremely rare. KNOW: different levels of coiling replication proteins NOTES TAKEN FROM: LEVELS OF CONDENSATION 1. Beads on a String The dna double helix winds twice around the histone core forming a nucleosome bead. A short strip of DNA (about sixty base pairs long) acts like a linking chain (hence linker DNA between adjacent nucleosomes. This step reduces the length of DNA by six times. 2. Further condenses into the solenoid: hollow center held together by H1/H1 interactions. 4/1/03 11:37 am 3. solenoids then condense into radial loops. the radial loops are tacked on to the scaffold protein. the tubes on the protein then condense further into a coil. 4. coiling 5. super coiling keeps coiling until it is in the shape of a chromosome (the final level of DNA condensation. During interphase DNA may stay in radial loops attached to the nuclear lamina. RNA polymerase works around the histone proteins. Called euchromatin. Gene rich- used genes that is! (Light bands on karyotype). the dark bands are tightly coiled because those genes are not actively producing proteins. Some stretches stay highly condensed... heterochromatin. Stain very dark (NOT often used genes) Barr bodies: the second X chromosome in females that is turned off. stains differently. Random which one is turned off except in kangaroos, koala, and wombats. Olympics test. bio10-genetics bio10-protein synthesis chem10- dna & rna chem10- dna replication