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Unformatted text preview: BIS101/Engebrecht 4/27/2010 Lecture12 Chromosome Structure DNA in cells is not naked, but is complexed in a high order structure with proteins. Chromatin refers to DNA in chromosomes associated with proteins. This has structural as well as functional significance. I showed you pictures of lysed phage T2 and lysed E. coli cell to demonstrate the amount of DNA that is packed into cells. Although bacterial chromosomes also have associated proteins, they are much less complex and we will confine our discussion to eukaryotic chromosomes. I showed you a human chromosome to give you some idea of how much DNA is contained in all of our cells. The human genome is 2 meters long and 2 nm in diameter, this length of DNA is within the nucleus of every cell in our bodies (with the exception of RBCs which are anucleated). Somehow the 2 meters of DNA is partitioned into 46 chromosomes, which are considerably smaller in length. Amazingly, one chromosome is made up of a single molecule of DNA. At metaphase, the DNA is highly compacted to prepare for chromosome segregation. In interphase it is less compacted to prepare for DNA replication and gene transcription. This property of chromosomes explains why investigators had a hard time accepting that chromosomes contained the blueprint of life because they disappeared during interphase. We now know that they were just not visible with the power of microscopes available at the time. How does the genome fit into the nucleus? The DNA is packaged at four different levels (see figures 3-20 & 3-22 in 8 th edition; 2-4 & 2-5 in 9 th edition): 1) The first level is the nucleosome. Nucleosomes are made up of an octomer of 2x 4 different histone proteins - H2A, H2B, H3 and H4. These proteins are very basic (positively charged) and therefore interact with the negatively charged phosphate backbone of DNA. Together these form the core particle in which 146 bp of DNA is wrapped around the octomer 2 times. These results in the bead on a string structure. 2) The second level of compaction uses the histone H1 protein to organize the nucleosomes into a 30nm fiber . 3) The 30 nm fibers connect via loops to form the 200nm fiber (the 3 rd level). 4) Finally, at the 4 th level, the chromosomes are further wound to form a 700nm fiber . This high level of compaction is necessary for chromosome segregation but some level of decompaction must occur for genes to be replicated and expressed. This alteration between compaction states is mediated by posttranslational modification of the histones that make up the core particle. The tails on the histone molecules can be acetylated, methylated, phosphorylated and/or ubiquinated. The relationships between these posttranslational modifications are complicated and it has been proposed that there is a histone code. Unlike the genetic code, this code has not been cracked. There are correlations between different modifications and the affect "If our strands of DNA were stretched out in a line, the 46 chromosomes making up t...
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