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• DNA and Chromosomes Genes are carried by Chromosomes Two plant cells visualized by light microscope, DNA stained with DAPI Chromosome in Cells DNA (deoxyribonucleic acid) AGTC Human 46 chromosomes 22 homologs, x, or x/y Experimental procedures demonstrating that DNA is the genetic material 1940s The Structure and Function of DNA • 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 1953 Watson and Crick determined the structure of DNA DNA and its Building Nucleotides: Guanine (G), Adenine (A), Cytosine (C), Thymine (T). Polarized strand, 5’->3’ Base inside, sugar outside DNA and its Building Antiparallel strands DNA Pairs A always pairs with T, and G with C, A-T two hydrogen bonds, G-C three hydrogen bonds DNA Double Helix 10.4 nucleutides/turn; 3.4 nm between nucleutides DNA to Protein Genome: 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 To carry the genomic information to daughter cells DNA Duplication Using itself as template Cell Nucleus, compartmentalized DNA activity Nuclear pores allow communication Nuclear lamina and cytoskeleton mechanically support the nucleus Chromosomal DNA and its Packaging • 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 Nterminal tails of Histones Human Chromosome Complex of DNA and protein is called chromatin 44 homologous chromosomes and 2 sex chromosomes Complementary DNA with different Dyes The arrangement of the full chromosome set is called karyotype Banding Pattern of human chromosomes Giemsa Staining Green line regions: centromeres Encoding ribosome The organization of genes of a human chromosome Conservation between human and mouse genomes Usually important genes are encoded by conserved regions Note: Human chromosome 1 and mouse chromosome 4 mouse human centromere Cell Cycle DNA molecule not only carries genetic information, but also undergoes conformational change Chromosomes exist through the cycle Mitotic and interphase chromosome Single chromosome can only be visible during mitosis Chromosomes at interphase and M phase Three important DNA sequences Telomere, replication origin, centromere DNA Molecules are highly condensed in chromosomes Nucleosomes of interphase under electron microscope Nucleosome: basic level of chromosome/chromatin organization Chromatin: protein-DNA complex Histone: DNA binding protein A: diameter 30 nm; B: further unfolding, beads on a string conformation Nucleosome Structures Histone octamer 2 H2A 2 H2B 2 H3 2 H4 X-ray diffraction analyses of crystals Structure of a nucleosome core particle Structural Organization of the Core Histones The Assembly of the Core Histones Notice the long tails of the octamer The bending of DNA in a nucleosome 1. Flexibility of DNAs: A-T riched minor groove inside and G-C riched groove outside 2. DNA bound protein can also help Zigzag model of the 30-nm chromatin fiber Irregularities in the 30-nm fiber Flexible linker, DNA binding proteins Structural modulators: H1 histone, ATP-driven Chromatin remodeling machine, covalent modification of histone tails The function of Histone H1 The function of Histone tails Chromatin Remodeling Cyclic Diagram for nucleosome formation and disruption Covalent Modification of core histone tails Acetylation of lysines Mythylation of lysines Phosphorylation of serines Histone acetyl transferase (HAT) Histone deacetylase (HDAC) Summary • • • • • • DNA, Chromosome Centromere, telomere, replication origin Nucleosome, Chromatin, Histone: H1, H2A, H2B, H3, H4 Histone octamer, DNA packaging DNA binding proteins, Histone modifications The Global Structure of Chromosomes • Some rare cases of interphase chromosomes, certain features maybe universal • Representative forms forming typical interphase chromosome • Chromosome at mitosis Lampbrush chromosomes (amphibian oocyte, immature eggs) A model for the structure of a lampbrush chromosome Chromomeres: highly condensed and in general not expressed until unfolding A polytene chromosome from Drosophila salivary gland Dark bands and interbands Electron Microscope image of Drosophila polytene chromosome Chromosome puffs Folding and refolding at a time course of 22 hours RNA synthesis in Chromosome puffs Red: newly synthesized BrUTP; Blue: old ones diffused RNA synthesis in Chromosome puffs RNA synthesis in Chromosome puffs Model of RNA synthesis in Chromosome puffs A model for the structure of an interphase chromosome Position Effects on Gene Expression Heterochromatin: condensed Euchromatin: loose Speculative Model for the heterochromatin at the ends of yeast chromosomes Sir: Silent information regulator binding to unacetylated histone tails 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 Two speculative models for how the tight packaging of DNA in heterochromatin can be inherited during chromosome replication The specialized nucleosome formed on centromeres Also belongs to heterochromatin The structure of a human centromere 1. Alpha satellite DNA sequence 2. Kinetochore inner plate 3. Kinetochore outer plate 4. Spindle microtubules The plasticity of human centromere formation A typical mitotic chromosome at metaphase SEM of a region near one end of a typical mitotic chromosome EM of a mitotic chromosome Chromatin Packing Condensin plays important roles The SMC (Structural Maintenance of Chromosomes) proteins in condensins Selective localization of two interphase chromosomes Chromosome 18 (red) and 19 (turquoise) 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) Summary • 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.