DNA, Chromatin Lecture Notes PDF

Lecture 37: DNA, Chromatin The Central Dogma of Molecular Biology Iclicker: How do you think the cell “knows” which strand to copy into RNA? The 2 strands have opposite “chemical properties” and only 1 direction can be read. Iclicker: Are there any exceptions to the central dogma in nature?...

Lecture 37: DNA, Chromatin The Central Dogma of Molecular Biology Iclicker: How do you think the cell “knows” which strand to copy into RNA? The 2 strands have opposite “chemical properties” and only 1 direction can be read. Iclicker: Are there any exceptions to the central dogma in nature? YES DNA Structure -DNA structure provides a mechanism (copying) for hereditary Called “Semi-Conservative” Polarity of DNA -Phosphate is the reason why DNA is an acid (contains a negative charge) 5’ end: phosphate group 3’ end: OH group (sugar) - 5’ and 3’ refers to carbons on the Deoxyribose sugar The 2’ is the “deoxy” Base Pairs - A-T and G-C base pairs form between each strand via hydrogen bonding The 2 strands are antiparallel! DNA (and RNA) sequences are always written down in the 5’ → 3’ Direction Helix -Each strand Twist to form a helix Function: minimizes the “stacking energy” ^ referring to the energy released by one base’s interaction with its adjacent bases on the same strand Iclicker: DNA Sequence: AATGGCTGGATCCCAATT, what is the sequence of the other strand? AATTGGGATCCAGCCATT -Because of its chemical structure, DNA double helices have major and minor grooves Important: PROs can contact bases from the major groove, permitting them to recognize short sequences of bases in DNA Binding of a Protein -The binding of a protein (Transcriptional Factor) to a specific DNA sequence occurs in the major groove of DNA Mainly through hydrogen bonding Nucleus -Most DNA is in the nucleus Structure of a Nucleus: Iclicker: Where else is DNA normally found in the cell besides the nucleus? Mitochondria Iclicker: Mitochondrial Mutations: inherited from mom or dad? From mom due to the egg containing the mitochondria Human Genome - The human genome contains 23 pairs of Chromosomes (46 total.) “Diploid” Chromosomes condense during mitosis (ONLY) At all other times they look like spaghetti -Every cell in the body contains the same 46 chromosomes with the exact DNA sequences as in every other cell, BUT there are 2 exceptions: 1.) Sperm and egg cells contain 23 chromosomes due to mitosis (“Haploid”) 2.) Antibody-Producing Immune Cells (B-Cells) Chromosomes Condense ONLY during mitosis Chromosomes need 3 elements to be stable: 1.)Centromere: Where the mitotic spindle attaches to pull chromosomes apart at mitosis 2.) Replication Origin: Where the cell initiates all other DNA replication 3.) Telomere: Allows the cell to copy the ends of the chromosome Heterochromatin vs. Euchromatin -Heterochromatin: DNA is generally not very active During interphase, is compact Has long stretches of repeat sequences called satellite DNA -Euchromatin: Generally more active During interphase, not very condensed Human Genome: Very Complex -Within each gene, this whole DNA sequence gets transcribed into RNA, BUT: Only the DNA sequences in yellow end up in the final RNA ^Called Exons The rest is splices out of the RNA ^Called Introns Transposons -Transposons: Mobile genetic elements that have multiplied in our genome by replicating themselves and inserting the new copies in different positions Chromatin -Chromatin: Consists of DNA Bound to both histone and non-histone proteins Histones -Histones: Tightly bound to DNA because histone are positively charged Nucleosomes -Nucleosomes: an octamer containing 2 of each core histone: 4 Core histones: H2A, H2B, H3, H4 -Nucleosomes get in the way of DNA-binding and DNA-Reading enzymes The cell addresses this using “Chromatin Remodeling Complexes” -Chromatin Remodeling Complexes: move nucleosomes around, allowing access of bases to transcription and replication proteins This complex pulls on the DNA of its bound nucleosome and loosens its attachment to the histone octamer, sliding the DNA and nucleosome in opposite directions -Attractions between nucleosomes compact the chromatin fiber Histone Tails Regulate Chromatin Compaction -Exit points of the 8 histones tails, 1 from each histone protein Tails are largely unstructured, suggesting that they are highly flexible The Histone tails mediate interactions between nucleosomes that help pack them together The linker Histone H1(sits between 2) also helps compact the nucleosomes Histone Modifications -DNA methylation and (chemical) histone modifications = EPIGENETIC MARKS They determine which genes have active vs. inactive chromatin stakes in a particular cell state DNA = HARDWARE EPIGENETIC MARKS = SOFTWARE -Certain Regions of Chromatin (Lamin-associated domains, RED) Recruit Chromatin to Nuclear lamin → Shuts off associated genes