Genetics Lecture 2 PDF

Genetics DNA Packaging LECTURE (2) DR. El-Sawy 0  Genetics DNA Packaging Genetic Diversity  Differe...

Genetics DNA Packaging LECTURE (2) DR. El-Sawy 0  Genetics DNA Packaging Genetic Diversity  Different arrangements of nucleotides in a nucleic acid ( provides the key to diversity among living organisms Some definitions :  The hereditary material of the cell DNA  Blueprint of life. Chromosome  Molecule of DNA.  Definition The functional units of DNA located on the chromosomes. Units of genetic material that codes for a specific trait.  Function DNA sequence that is needed to encode a a sequence of a Gene protein or a character  Number Total number is more than 100 000 in mammals  Size: Humans: average = 3000 bp & largest = 2.4 million bp DR. El-Sawy 1  Genetics DNA Packaging Introduction :  Total length of DNA (all chromosomes of human cells) =1.8 meters.  Nucleus diameter = 6 μm.  DNA packaging :to fit this large amount of DNA into the chromosomes in the nucleus and still be functional.  Site: In eukaryotic cells: e.g human cells, a DNA molecule is a linear helix tightly packaged into a chromosome.  Timing : prophase of mitosis prior to being separated into daughter cells.  Double stranded DNA molecule together with associated proteins. Def  DNA is tightly packed around histones & other DNA binding proteins. Euchromatin Heterochromatin  Less densely packed DNA.  More tightly packed DNA.  Available for gene expression  With areas of limited gene Types (active genes). expression (as genes become not accessible to various enzymes & factors). DR. El-Sawy 2  Genetics DNA Packaging  Positively charged proteins: high content of basic amino acids (Arginine, Histidine & Lysine)  Form ionic bonds with - ve charged phosphate group of DNA Basic histone to form the basic structural units called nucleosomes. proteins:  5 types: H1 H2A - H2B H3 - H4.  Structural proteins: for packaging of DNA into chromatin. Non histone  Enzymes: for DNA packaging, replication & transcription. proteins:  Regulatory factors: for replication & transcription. Levels of eukaryotic DNA organization 1. Nucleosomes. 2. 10-nm chromatin fibril. Euchromatin 3. 30 -nm chromatin fiber. 4. 700 -nm chromatid. heterochromatin 5. 1400 -nm chromosome. DR. El-Sawy 3  Genetics DNA Packaging  Beads-on-a-string. Character  Simplest unit of DNA-protein interaction. 1. Contains disc- core proteins: octamer 8 subunits (2 molecules of each H2A, H2B, H3, H4). 2. 1.75 turns of DNA double helix (146 base pairs) wrapped round core Nucleosome Structure proteins. 3. Connected by small pieces of DNA (50 bp Long) called linker DNA to which H1 histone is associated. 4. The formed DNA-protein disc is 11nm in diameter & 5 nm high.  Protects DNA from digestion by Function nucleases. 10-nm  Packing ratio: 10 folds. chromatin  Linker DNA & H1: facilitates packing of nucleosomes to fibril: more compact structure. DR. El-Sawy 4  Genetics DNA Packaging  Packing ratio: 50 folds. 30-nm  Supercoiling of 11 nm fibril with 6-7 nucleosomes per chromatin turn. fiber  It is stabilized by H1 histones.  Packing ratio: 8000 fold.  Supercoiling of 30nm fibril into twisted- looped structures 700-nm  Every 6 loops are wrapped around a supporting matrix chromatid of scaffold non-histone proteins rosettes.  Each 30 rosettes form 1 turn of a coil that forms each chromatid.  Packing ratio: 10000 fold to generate the chromosomes.  Identified initially at the prophase under microscope. 1400-nm  Each chromosome is formed of 2 identical sister chromosome chromatids connected at centromere.  Numbered according to length & position of centromere. DR. El-Sawy 5  Genetics DNA Packaging DR. El-Sawy 6  Genetics DNA Packaging  AT-rich region (up to 106 bp long). Def  Binds certain proteins to form kinetochore (a complex that can binds the mitotic spindle).  Forms the ‘‘arms’’ of chromosome: p → the shorter. q → the longer. Position  The ends of each chromatid consists of tandem repeats of (5’- TTAGGG-3’ sequences called Telomeres (many kilos bp long).  Become more shorter in aging and cancer Chromosomes number : Somatic cells Germ cells  Any cell not part of germ line  Gamete i.e Sperm or ovum  Genome is diploid  Genome is haploid  23 pairs of chromosomes.  23 chromosomes only. DR. El-Sawy 7  Genetics DNA Packaging  Fayza is a 36 years old woman, presented with facial butterfly rash, polyarthritis and general malaise.  She is a Systemic Lupus Erythematosus patient.  Laboratory diagnosis revealed presence of anti-histone antibodies. Q : Case report and clinical correlates ?  Histones are complexes of proteins, around which DNA is stored.  Anti-Histone Antibodies may target the histone complex or any of the protein subunits shown here DR. El-Sawy 8