DNA and ChromosomesNucleotides are composed of a base, sugar, and phosphate group. • In deoxyribonucleic acid (DNA), the sugar is deoxyribose. phosphate base sugar P O O O CH2 H OH H H H H OH HO C N CH N C C N HC N NH2• Nucleotides are linked via phosphodiester bonds to form nucleic acids – phosphodiester bonds form via condensation reactions • DNA nucleotides can be purines (G/A) or pyrimidines (T/C) • DNA strands have a polarity (5’ versus 3’) • DNA strands are negatively charged• Double-stranded DNA consists of two complementary chains of nucleotides in an anti-parallel conformation • The DNA stands are held together by hydrogen bondsThe DNA double helix contains 10 base pairs (bp) per turn.Most genes contain information to make proteins• A genome is all the information contained within an organism's DNA • Eukaryotic DNA is divided into chromosomes – homologous chromosomes (homologues): one pair of chromosomes; one maternal and one paternal • Karyotype: display of the mitotic chromosomesHuman Genome (draft sequence 2001, finished 2004) • 22 autosomes and 2 sex chromosomes • 3.2 billion base pairs • approximately 25,000 genes • 1.5% of the genome encodes exonsThe duplication and segregation of chromosomes occurs through an ordered cell cycleThree DNA sequence elements ensure chromosomes can be replicated (replication origin and telomere) and segregated (centromere).Chromosomes in a cell are condensed. mitotic chromosomes: most condensed interphase chromosomes: less condensed Chromatin: DNA and its associated proteinsNucleosomes are the basic unit of chromatin packing. – consist of 4 pairs of histones (8 total) • Histones are highly conserved, small, positively charged proteins – 147 bp piece of DNANucleosomes are further packed into 30 nm fibers via: 1. interactions between histone tails 2. binding of histone H1Nucleosome-wrapped DNA is accessible to other DNA binding proteins via: 1. nucleosome structure is fluid and dynamic 2. chromatin remodeling complexes slide DNA in nucleosomes in an ATP dependent mannerNucleosome-wrapped DNA is accessible to other DNA binding proteins via: 3. Modification of histone tails by modifying proteins • disrupts stability of the 30 nm fibers and higher order packing • recruits proteins that condense or decondense chromatinThe pattern of histone modification indicates the status of the nearby chromatin.There are two levels of interphase chromatin condensation. 1. heterochromatin – most condensed – induced by tail modifications, including methylation of lysine 9 on the histone H3 tail – gene poor regions (centromeres and telomeres) – genes are not expressedHeterochromatin example: X inactivationThere are two levels of interphase chromatin condensation. 2. euchromatin – less condensed – gene rich regionsGenes undergoing transcription are found in areas of chromatin with the least amount of condensation.Chromatin structure is inherited (epigenetic inheritance).DNA is contained within the nucleus of eukaryotic cells. - nuclear envelope: two co-centric lipid bi-layers - nuclear pores: allow exchange between the cytoplasm and nucleus - nuclear lamina: mesh of intermediate filaments that support the nucleusChromosomes occupy discrete territories within the nucleus.There are biochemical neighborhoods within a nucleus.Nucleolus: example of a “biochemical neighborhood”. • Nucleolus: contains genes that encode ribosomal
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