dna and chromosomes. chromosome in cells dna (deoxyribonucleic acid) agtc human 46 chromosomes 22...
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• DNA and Chromosomes
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Chromosome in CellsDNA (deoxyribonucleic acid)
AGTCHuman 46 chromosomes22 homologs, x, or x/y
Genes are carried by Chromosomes
Two plant cells visualized by light microscope, DNA stained
with DAPI
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Experimental procedures demonstrating that DNA is the genetic material1940s
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• Genetic information is carried in the linear sequence of nucleotides in DNA
• Genetic information contains instructions to synthesize proteins
• DNA forms double helix with two complimentary strands holding together by hydrogen bonds between A-T (2 bonds) and G-C (3 bonds)
• DNA duplication occurs using one strand of parental DNA as template to form complimentary pairs with a new DNA strand.
• DNA is in nucleus in eucaryotes
The Structure and Function of DNA
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1953 Watson and Crick determined the structure of DNA
DNA and its BuildingNucleotides: Guanine (G), Adenine (A), Cytosine (C),
Thymine (T).Polarized strand, 5’->3’
Base inside, sugar outside
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DNA and its BuildingAntiparallel strands
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DNA PairsA always pairs with T,
and G with C,A-T two hydrogen bonds, G-C three hydrogen bonds
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DNA Double Helix10.4 nucleutides/turn; 3.4 nm between nucleutides
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DNA to ProteinGenome: the complete set of information in an organism’s DNA
Total length of DNA about 2 meters long in a human cell, encoding about 30000 proteins
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To carry the genomic information to daughter cellsDNA Duplication
Using itself as template
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Cell Nucleus, compartmentalized DNA activity
Nuclear pores allow communicationNuclear lamina and cytoskeleton mechanically support the nucleus
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• A gene is a nucleotide sequene in a DNA molecule that act as a functional unit for protein production, RNA synthesis.
• Introns and Exons• Chromosome: single long DNA contains a linear array of
many genes. • Human genome contains 2.3x109 DNA nucleotide pairs, with
22 different autosomes and 2 sex chromosomes.• Chromosomal DNA: replication origins, telomeres,
centromeres• Histones form the protein core for DNA wrapping• Nucleosome: repeating array of DNA-protein particles• Modification of Chromatin and nucleosomes: histone H1,
ATP-driven chromatin remodeling complexes, and enzymatically catalyzed covalent modification of the N-terminal tails of Histones
Chromosomal DNA and its Packaging
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Human ChromosomeComplex of DNA and protein is called chromatin
44 homologous chromosomes and 2 sex chromosomesComplementary DNA with different Dyes
The arrangement of the full chromosome set is called karyotype
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Banding Pattern of human chromosomes
Giemsa StainingGreen line regions:
centromeres
Encoding ribosome
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The organization of genes of a human chromosome
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Conservation between human and mouse genomesUsually important genes are encoded by conserved regions
Note: Human chromosome 1 and mouse chromosome 4
human mousecentromere
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Cell CycleDNA molecule not only carries genetic information, but also undergoes
conformational changeChromosomes exist through the cycleMitotic and interphase chromosome
Single chromosome can only be visible during mitosis
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Chromosomes at interphase and M
phase
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Three important DNA sequencesTelomere, replication origin, centromere
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DNA Molecules are highly condensed in chromosomesNucleosomes of interphase under electron microscope
Nucleosome: basic level of chromosome/chromatin organization Chromatin: protein-DNA complex
Histone: DNA binding proteinA: diameter 30 nm; B: further unfolding, beads on a string conformation
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Nucleosome StructuresHistone octamer
2 H2A2 H2B2 H32 H4
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X-ray diffraction analyses of crystalsStructure of a nucleosome core particle
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Structural Organization of the Core Histones
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The Assembly of the Core Histones
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Notice the long tails of the octamer
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The bending of DNA in a nucleosome1. Flexibility of DNAs: A-T riched minor groove inside and G-C
riched groove outside2. DNA bound protein can also help
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Zigzag model of the 30-nm chromatin fiber
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Irregularities in the 30-nm fiberFlexible linker, DNA binding proteins
Structural modulators: H1 histone, ATP-driven Chromatin remodeling machine, covalent modification of histone tails
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The function of Histone H1
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The function of Histone tails
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Chromatin Remodeling
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Cyclic Diagram for nucleosome formation and
disruption
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Covalent Modification of core histone tails
Acetylation of lysinesMythylation of lysines
Phosphorylation of serines
Histone acetyl transferase (HAT)
Histone deacetylase (HDAC)
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• DNA, Chromosome
• Centromere, telomere, replication origin
• Nucleosome, Chromatin,
• Histone: H1, H2A, H2B, H3, H4
• Histone octamer, DNA packaging
• DNA binding proteins, Histone modifications
Summary
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• Some rare cases of interphase chromosomes, certain features maybe universal
• Representative forms forming typical interphase chromosome
• Chromosome at mitosis
The Global Structure of Chromosomes
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Lampbrush chromosomes (amphibian oocyte, immature eggs)
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A model for the structure of a lampbrush chromosome
Chromomeres: highly condensed and in general not expressed until
unfolding
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A polytene chromosome from Drosophila salivary glandDark bands and interbands
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Electron Microscope image of Drosophila polytene chromosome
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Chromosome puffsFolding and refolding at a time
course of 22 hours
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RNA synthesis in Chromosome puffsRed: newly synthesized BrUTP; Blue: old ones diffused
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RNA synthesis in Chromosome puffs
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RNA synthesis in Chromosome puffs
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Model of RNA synthesis in Chromosome puffs
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A model for the structure of an interphase chromosome
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Position Effects on Gene Expression
Heterochromatin: condensedEuchromatin: loose
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Speculative Model for the heterochromatin at the ends of yeast chromosomes
Sir: Silent information regulator binding to unacetylated histone tails
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Speculative Model for the heterochromatin at the ends of yeast chromosomes
DNA-binding proteins recognize DNA sequence close to telomere, recruit Sir proteins and cause histone tail modification, forming heterochromatin
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Two speculative models for how the tight packaging of DNA in heterochromatin can be inherited during chromosome replication
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The specialized nucleosome formed on centromeresAlso belongs to heterochromatin
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The structure of a human centromere
1. Alpha satellite DNA sequence
2. Kinetochore inner plate3. Kinetochore outer plate4. Spindle microtubules
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The plasticity of human centromere formation
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A typical mitotic chromosome at metaphase
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SEM of a region near one end of a typical mitotic
chromosome
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EM of a mitotic chromosome
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Chromatin PackingCondensin plays important roles
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The SMC (Structural Maintenance of Chromosomes) proteins in
condensins
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Selective localization of two interphase chromosomesChromosome 18 (red) and 19 (turquoise)
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Specific regions of interphase chromosomes in close proximity to the nuclear envelope
Two different regions of chromosome 2 (yellow and magenta) close to the nuclear envelop (green)
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• Chromosomes are decondensed during interphase and hard to visualize
• Lampbrush chromosomes of vertebrate oocytes and polytene chromosomes in the giant secretory cells of insects are exceptions, revealing the global organization of chromosome
• Gene expression needs the decondensation of chromosome loops
• Euchromatin and heterochromatin• Telomere and centromere are general heterochromatin• Chromosomes are spatially organized and deposited in
nucleus• Mitotic chromosomes are condensed and organized.
Summary