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Genetics Lecture No. 2.docx

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Western University
Biology 2581B
Jim Karagiannis

Genetics Lecture No. 2: The Eukaryotic Chromosome th Monday January 14 , 2013 Introduction: -The human diploid genome is comprised of around 6 billion base-pairs in a double-helix 2 nm in width. The total length of the human genome is 2m and the processes that are undergone at the DNA level have profound effects on the cellular level. In the basic model of DNA structure, each turn of the helix is about 34 Angstroms in length and 20 Angstroms in width. Major and minor grooves result from the geometry of base pairing taking place. The angle between the glycosidic bonds of the minor groove is 120 degrees, while the angle between the glycosidic bonds of the major groove is 240 degrees. The Flexibility Of DNA Structure: -DNA is biologically present in two basic conformations: B-DNA (right-handed helix) and Z-DNA (left-handed helix). B-DNA has a smoother shape and swirls in a clockwise direction from a bird’s-eye perspective. Z-DNA is more jagged in appearance with larger major grooves and smaller minor grooves. Of the two B-DNA is the predominant form found in vivo and Z-DNA occurs only transiently in an organism. A-DNA is a form of DNA that occurs in vitro alone and is therefore not physiologically relevant. Biological Function Of Z-DNA: -Evidence suggests that Z-DNA may have a biological role within cells. Z-DNA is formed transiently in association with transcription and there are several virus proteins (essential for virulence) identified with highly-specific Z-DNA binding activities. Antibodies also bind to Z-DNA in its transcriptionally active regions. It is still not clear what the role of Z-DNA actually is. Flexibility In Helical Structure & Base Flipping: -A crucial property of the double helix is its ability to separate the two strands without disrupting covalent bonds. This makes it possible for the strands to separate and reform under physiological conditions. This is important for the processes of DNA replication, transcription, and also for DNA repair mechanisms. In base flipping, enzymes involved in DNA repair may scan for DNA lesions by “flipping out” bases and make repairs if needed. Flexibility In DNA Organization & DNA Topology: -In their organization of DNA, humans have a linear double-stranded chromosome and mitochondria and bacteria have a circular genome. Viruses display lots of variation in DNA organization. DNA topology refers to the molecule’s orientation in space. Circular DNA molecules, as opposed to linear DNA molecules, are topologically-constrained (inability to denature a strand due to the interwoven qualities of the two strands). Linear DNA molecules can become topologically constrained if binding proteins are present on the molecule. For a constrained double-helix, torsional stress introduces supercoiling. Overwound DNA strands introduce + (toroidal) writhe and results in + supercoiling (molecule has + superhelicity). Underwound DNA strands introduce – (plectonemic) writhe and results in – supercoiling (molecule has – superhelicity). DNA Supercoiling: -In a relaxed (energetically-favourable) state, DNA has about 10.5 base-pairs for every turn of the double helix. Thus, for a DNA fragment 260 base-pairs long, the two DNA strands would cross each other 25 times. This [25] is referred to as the linking number. The process of unwinding destabilizes the double-helix at 11.3 base-pairs per turn (not energetically- favourable). The strands can be stabilized in one of two ways, they either come apart or supercoils are introduced. The reason why living cells store their DNA with negative superhelicity is because there are many instances when it is advantageous to drive the unwinding of the double-helix (the energy stored could aid in processes of strand separation like replication and transcription). Negative supercoiling is also useful in making the DNA mole
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