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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
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 Pairs A always pairs with T, and G with C, A-T two hydrogen bonds, G-C three hydrogen bonds
DNA to Protein Genome: the complete set of information in an organisms 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
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
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
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
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
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
Chromatin Remodeling
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
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
RNA synthesis in Chromosome puffs Red: newly synthesized BrUTP; Blue: old ones diffused
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 structure of a human centromere 1. Alpha satellite DNA sequence 2. Kinetochore inner plate 3. Kinetochore outer plate 4. Spindle microtubules
EM of a mitotic chromosome
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.