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Download Composition and structure of DNA and RNA and differences
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Composition and structure of DNA and RNA and differences between two o DNA DNA structure: Base –purine (A, G) or pyrimidine (C, T) Sugar deoxyribose (lacks –OH at C2) Phosphate—PO4 forms “backbone” Nucleoside: purine/pyrimidie base + sugar linked by N-glycosidic bond Nucleotide: purine/pyrimidie base + sugar + PO4 (ester linkage at 5’ –OH group) DNA base pairing o A-T, 2H bond o C-G, 3H bond DNA polarity o 5’ phosphate to 3’ free hydroxyl 3’ hydroxyl where new nucleotide can be added via phosphodiester bond Double helix is coiled around axis of symmetry Paired in anitparrallel fashion Major and minor grooves o Major groove major site of protein binding also aided by negative charge o Certain anticancer drugs such as dactinomycin (atinomycin D), exert a cytotoxic effect by intercalating into the narrow grove and interfering with DNA synthesis. RNA structure o Different from DNA Major difference is hydroxyl of 2’ sugar Minor difference use of Uracil instead of thymine o Structure: RNA chains are usually single-stranded and lack continuous helical structure RNA can have considerable secondary structure and tertiary structure because base pairs can form in regions where the strand loops back on itself DNA damage o Both heat and alkali (base) cause the two strands of the double helix to separate o Alkali (base) will not break the phosphodiester bonds of DNA, but it will cleave phosphodiester bonds of RNA o Heat alone converts double-stranded DNA to single-stranded DNA o Separation of DNA strands is called “melting” and the temperature at which 50% of the DNA is separated is call the Tm. DNA with a high content of GC= higher Tm Hybridization of DNA/RNA o Seen during transcription process o mRNA can also inhibit transcription through binding The Central Dogma Forms of DNA o The B form is a right-handed helix with ten residues per 360o turn of the helix, and with the planes of the bases perpendicular to the helical axis. Chromosomal DNA is thought to consist primarily of B DNA o The A form is a right-handed helix but there are 11 bases per turn and the planes of the base pairs are tilted 20o away from the perpendicular to the helical axis. The conformation found in DNA-RNA hybrids is probably close to the A form. o Z-DNA is a left-handed helix that contains about 12 bases per turn. The deoxyribose-phosphate backbone zigzags (hence the name Z-DNA). Transitions between the B and the Z helical forms of DNA may have a role in regulating gene expression. Chromosome structure o Histones: Protein core made of 2 H2A, H2B, H3 and H4 along with H1 linker o Centromeres: Spindle fibers attach during mitosis and meiosis here If you lack centromere chromosome can be lost during mitosis o Telomeres Protect ends from degradation or fusion Structure of chromosomes (role of histones, nucleosomes, etc) o Linear double strand helix> supercoil> chromatin-DNA helix + histones= nucleosome> solenoids (loops)> chromosome > genome Forms and functions of RNA (mRNA, rRNA, tRNA) miRNAs role in normal cell regulation activity, some associated with cancer Eukaryotic tRNA o 20 different tRNAs Eukaryotic rRNA o Riobosome o Cytoplasmic ribosomes in eukaryotes 4 types:18S, 28S, 5S and 5.8S >> 80S Prokaryotic ribosomes contain three types of rRNA molecules with sedimentation coefficients of 16, 23, and 5S (dependent on density and shape of complex) >> 70 S Mitochondria >> 70S properties, 55S Identify structure and function of genes o Eukaryotic mRNA consists of A leader sequence at the 5’-end A trailer sequence at the 3’-end The leader sequence begins with a guanosine cap structure at its 5’ end (added after transcription) The coding region begins with the trinucleotide start signal of translation or AUG (initiating methionine) Translation ends via a termination signal. The trailer sequence terminates at its 3’-end with a poly (A) tail up to 200 nucleotides in length (added after transcription) Identify the life cycle of a retrovirus Know the clinical uses of azidthymidine, doxorubicin and 5-FU—site and mechanism of action o Erythromycin (a macrolide antibiotic) acts by inhibition of protein synthesis in susceptible organisms reversibly binds to 50 S ribosomal subunits (prokaryotes) causing inhibition of translocation of aminoacyl transfer-RNA (stops protein synthesis o 5-fluorouracil (5-FU) pyrimidine base similar in structure to uracil (RNA) and thymidine (DNA) inhibits synthesis of thymidine nucleotides used for DNA replication thymidylate synthase (TS) converts dUMPdTMP the active form of 5-FU converts to5-FdUMP that irreversibly binds TS used in chemotherapy to “knockdown” DNA synthesis----cell replication o Doxorubin: DNA intercalator Anthracycline antibiotic: works by intercalating into the DNA interior and disrupting the helix---used as a chemotherapy agent; disrupts DNA replicationcell replication o Azidothymidine: anti-retroviral AZT is the first drug approved for treatment of AIDS and HIV infection A reverse transcriptase inhibitor (enzyme used by HIV to make a copy of it’s RNA genome Also inhibits DNA polymerase γ (may produce the side effects) Does not destroy infection Has adverse side effects Frequently used in combination therapy