DNA and chromosomes

• Chromosomal DNA: replication origins, telomeres, centromeres • Histones form the protein core for DNA wrapping • Nucleosome: repeating array of DNA-protein particles • Modification of

• DNA and

Chromosomes

Chromosome in Cells

DNA (deoxyribonucleic acid)

AGTCHuman 46 chromosomes

22 homologs, x, or x/y

Genes are carried by

ChromosomesTwo plant cells visualized by

light microscope, DNA stained

with DAPI

Experimental procedures demonstrating that DNA is the genetic material

1940s

• Genetic information is carried in the linear sequence of

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

1953 Watson and Crick

determined the structure of DNA

DNA and its Building

DNA and its Building

Antiparallel strands

DNA Double Helix10.4 nucleutides/turn; 3.4 nm between nucleutides

DNA to ProteinGenome: the complete set of information in an organism’s DNATotal length of DNA about 2 meters long in a human cell, encoding

about 30000 proteins

To carry the genomic information to daughter cells

DNA DuplicationUsing itself as template

Cell Nucleus, compartmentalized

DNA activityNuclear pores allow communication

Nuclear lamina and cytoskeleton

mechanically support the nucleus

• 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

Human ChromosomeComplex of DNA and protein is called chromatin

44 homologous chromosomes and 2 sex chromosomes

Complementary DNA with different DyesThe arrangement of the full chromosome set is called karyotype

The organization of genes of a human chromosome

Conservation between human and mouse genomes

Usually important genes are encoded by conserved regionsNote: Human chromosome 1 and mouse chromosome 4

centromere

Cell CycleDNA molecule not only carries genetic information, but also undergoes

conformational changeChromosomes exist through the cycleMitotic and interphase chromosomeSingle 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 chromosomesNucleosomes of interphase under electron microscopeNucleosome: basic level of chromosome/chromatin organization

Chromatin: protein-DNA complexHistone: DNA binding proteinA: diameter 30 nm; B: further unfolding, beads on a string conformation

X-ray diffraction analyses of crystalsStructure 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 fiberFlexible linker, DNA binding proteinsStructural 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

• DNA, Chromosome

• Centromere, telomere, replication origin

• Nucleosome, Chromatin,

• Histone: H1, H2A, H2B, H3, H4

• Histone octamer, DNA packaging

• DNA binding proteins, Histone modifications

Summary

• Some rare cases of interphase chromosomes, certain features maybe universal

• Representative forms forming typical interphase chromosome

• Chromosome at mitosis

The Global Structure of Chromosomes

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 puffsRed: 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

ExpressionHeterochromatin: condensed

Euchromatin: loose

Speculative Model for the heterochromatin at the ends of yeast

chromosomesSir: Silent information regulator binding to unacetylated histone tails

Speculative Model for the heterochromatin at the ends of yeast

chromosomesDNA-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 envelopeTwo different regions of chromosome 2 (yellow and magenta) close to

the nuclear envelop (green)

• 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