Topic 19

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Biochemistry 2280A
Chris Brandl

Topic 19 Topic 19 – Chromatin Human DNA must be condensed - human genome about 3 x 10^9 base pairs long - at 0.34nm/bp in double helix, ~102cm - two copies of each chromosome per cell  about 2m of DNA in each cell - human DNA must be condensed by about 10,000 fold to fit inside nucleus Way to condense -best analogy for most fundamental unit of packaging of DNA double helix? a) ball of twin  no because can’t get at first bit of twin b) string of beads c) spool of thread d) bowl of spaghetti e) telephone DNA packaging is highly organized - Despite DNA being condensed, DNA must remain available for replication, repair, and gene transcription - Eukaryotic DNA condensed with help of specialized proteins  chromatin  Bacteria condense DNA but in a different way - Protein/DNA complex is called chromatin Histones - primary eucaryotic proteins involved in condensing DNA (prokaryotes use different proteins) - small proteins – contain fewer than 200 aa - rich in lysine and arginine residues (+ charged to interact with negatively charged DNA)  Lysine and arginine can become protonated and be positively charged at physiological pH – ideally suited to interact with negatively charged phosphate of DNA - 5 types of histones: H1, H2A, H2B, H3, H4  All types different sequences, but similar properties - DNA makes 1.7 circuit around histone core, Lysine and Arginine make up more of histone than average protein – 2-3 times as rich of L and A Conservation of Histone H4 - histones required to package DNA into cell – very important function, so large conservative sequence - same across a bunch of species - conservative mutation – change but still same charge as original, so no change in properties - hardly ever see proteins this similar - sequence preserved  entire sequence is important for protein function 1 Topic 19 Histone Octamers - contain 2 copies each of histones H2A, H2B, H3, H4 - DNA double helix wraps around histone octamer edge (kind of looks like a hockey puck) 1.65 times (146bp) - Wrapped DNA and histone called nucleosome core particle - DNA negative and histones positive  wrap closely - Make the DNA strand shorter  Similar to spool of thread - Each different colour represents different histone Nucleosomes - Histone octamers are called nucleosome core particles - Core particles (about 146 residues) are linked by stretches of DNA 3-80 bp (~50bp) long  so in total core particle and linker about 200 bp  beads on string join by linker region - nucleosome  core particle + linker region - nucleosomes compact DNA strand by factor of about 3 30nm chromatin fibres  called that because that is their thickness  nucleosome compact into coil called 30nm chromatin fibre - second level of DNA packaging  requires histone H1 - stabilizes  structure still controvers
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