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1- B DNA -- Genome 2- Double helix -- Relaxed form 3- Antiparallel -- Super coil 4- Major groove -- Histone like proteins 5- Minor groove -- Nucleosome.

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Presentation on theme: "1- B DNA -- Genome 2- Double helix -- Relaxed form 3- Antiparallel -- Super coil 4- Major groove -- Histone like proteins 5- Minor groove -- Nucleosome."— Presentation transcript:

1 1- B DNA -- Genome 2- Double helix -- Relaxed form 3- Antiparallel -- Super coil 4- Major groove -- Histone like proteins 5- Minor groove -- Nucleosome 6- Sugar puckering -- Nucleosome core 7- C2 endo --Chromatin 8- C3 Exo -- Linker 9- Syn, Anti -- Sscaffold --Right handed -- Solenoid 10- A DNA, C3 endo position --Melting point 11- Z DNA -- Left handed, G and A in syn position -- G and (A) in C3 endo position -- Base stacking --Hydrogen bond -- Phosphate position -- Hoogsteen Base pair -- Triple stranded helix

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5 Hypochromism. (A) Single-stranded DNA absorbs light more effectively than does double-helical DNA. (B) The absorbance of a DNA solution at a wavelength of 260 nm increases when the double helix is melted into single strands.

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8 StepMelting ΔG /Kcal mol -1 T A-0.12 T G or C A-0.78 C G-1.44 A G or C T-1.29 A A or T T-1.04 A T-1.27 G A or T C-1.66 C C or G G-1.97 A C or G T-2.04 G C-2.70

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10 Structural ParameterA-DNAB-DNAZ-DNA Direction of helix rotation Right handed Left handed Residue per helical turn 111012 Pitch (length) of the helix 28.2 Å34 Å44.4 Å Base pair tilt20°-1°7° Rotation per residue32.7°34.3°-30° Diameter of helix23 Å20 Å18 Å Configuration dA, dT, dC anti of glycosidic bond dGanti syn Sugar Pucker dA, dT, dC C3' endoC2' endo dGC3' endoC2' endoC3' endo Topology of major groove Narrow, deepWide, deepFlat Topology of minor groove Broad, shallowNarrow, shallowNarrow, deep

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12 Major- and Minor-Groove Sides. Because the two glycosidic bonds are not diametrically opposite each other, each base pair has a larger side that defines the major groove and a smaller side that defines the minor groove. The grooves are lined by potential hydrogen-bond donors (blue) and acceptors (red).

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22 Propeller Twist. The bases of a DNA base pair are often not precisely coplanar. They are twisted with respect to each other, like the blades of a propeller.

23 Axial View of DNA. Base pairs are stacked nearly one on top of another in the double helix

24 StepStacking ΔG /kcal mol -1 T A-0.19 T G or C A-0.55 C G-0.91 A G or C T-1.06 A A or T T-1.11 A T-1.34 G A or T C-1.43 C C or G G-1.44 A C or G T-1.81 G C-2.17

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42 Histone a Molecular weight Number of amino acidsamino acids Percentage Lysine + Arginine H122,50024430.8 H2A13,96012920.2 H2B13,77412522.4 H315,27313522.9 H411,23610224.5 a Data are for rabbit (H1) and bovine histones.

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49 Structure of Histone Acetyltransferase. The amino-terminal tail of histone H3 extends into a pocket in which a lysine side chain can accept an acetyl group from acetyl CoA bound in an adjacent site

50 Histone modifications Histone proteins can undergo various types of modification, the best studied of these being histone acetylation.histone acetylation – the attachment of acetyl groups to lysine amino acids in the N-terminal regions of each of the core molecules. These N termini form tails that protrude from the nucleosome core octamer and their acetylation reduces the affinity of the histones for DNA and possibly also reduces the interaction between individual nucleosomes that leads to formation of the 30 nm chromatin fiber Histone acetyltransferasesHistone acetyltransferases (HATs) – the enzymes that add acetyl groups to histones. Histone acetylation plays a prominent role in regulating genome expression. The tails of the core histones also have attachment sites for methyl and phosphate groups and for the common (‘ubiquitous') protein called ubiquitin.ubiquitin Ubiquitination of histone H2B is part of the general role that ubiquitin plays in control of the cell cycle. Phosphorylation of histone H3 and of the linker histone has been associated with formation of metaphase chromosomes Methylation of a pair of lysine amino acids at the fourth and ninth positions from the N- terminus of histone H3. Methylation of lysine-9 forms a binding site for the HP1 protein which induces chromatin packaging and silences gene expression

51 Methylation of lysine-4 has the opposite effect and promotes an open chromatin structure Lysine-4 methylation is closely correlated with acetylation of histone H3 Two types of modification may work hand in hand to activate regions of chromatin. Remodeling is induced by an energy-dependent process that weakens the contact between the nucleosome and the DNA with which it is associated. Three distinct types of change can occur Remodeling, in the strict sense, involves a change in the structure of the nucleosome, but no change in its position. Sliding, or cis-displacement, physically moves the nucleosome along the DNA Transfer, or trans-displacement, results in the nucleosome being transferred to a second DNA molecule the proteins responsible for nucleosome remodeling work together in large complexes. One of these is Swi/Snf, made up of at least 11 proteins, which is present in many eukaryotes

52 Direct methylation of DNA also has a silencing effect Silencing can be implemented is by removing acetyl groups from histone tails This is the role of the histone deacetylases (HDACs).histone deacetylases HDACs are contained in multiprotein complexes. One of these is the mammalian Sin3 complex, which comprises at least seven proteins, including HDAC1 and HDAC2 along with others that do not have deacetylase activity but which provide ancillary functions essential to the process Both Sin3 and NuRD contain proteins that bind to methylated DNA.


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