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Gene/Genomes (DNA replication (Characteristics (Watson-Crick proposal…

- - - - Produce 2 complementary daughter strands
      - Gradual separation of 2 strands
      - Parental strands = template
    - - Original DNA = heavy DNA (15N)
        
        1st generation: 15N/N14 = hybrid
    - - Leading strand
        
        synthesize continuously
      - Lagging strand
        
        synthesize discontinuously
        
        Okazaki fragments
        
        Req: primers for each fragment
    - - Spontaneous mutation rate
        
        error rate of incorporation of incorrect nucleotide during replication
        
        low error rate (10^-9)
      - Based on geometry of base pair
      - Mechanisms:
        
        selection of nucleotide
        
        Proofreading
        
        Mismatch repair
    - - HIstones = intact in old & new histones = randomly distributed
      - DNA - nucleosome = rapid assembly
        
        Req: network of accessory proteins
  - - - Ahead of replication fork
        
        DNA gyrase (topoisomerase II)
        
        Relieve tension = ATP hydrolysis
        
        Positively supercoiled => negatively supercoiled
      - At replication fork
        
        Single-stranded DNA binding protein (SSB)
        
        Stablizing DNA
        
        Helicase
        
        Unwind parental duplex
    - - DNA polymerase
        
        DNA polymerase III
        
        Func: Adds nucleotides to 3' OH end of growing DNA
        
        Polymerization process
        
        Direction of polymerization: 5'-3'
        
        -OH gr at 3' of primer
        
        nucleophilic attach
        
        1 more item...
        
        Req: primer
        
        Structures
        
        Thumb
        
        Palm
        
        Exo
        
        Fingers (Pol)
        
        Beta clamp
        
        DNA polymerase I
        
        Func
        
        Replaces RNA (primers) with DNA
        
        DNA repair
      - DNA ligase
        
        seals the gap
        
        joined Okazaki fragments on lagging strand
      - Primase
        
        assembles RNA primers
        
        To initiate replication
        
        Direction of synthesis: 5'-3'
    - - Endonucleases
        
        Make internal cuts in nucleic acids
      - Exonucleases
        
        Types
        
        5'-3' exonuclease
        
        Role: remove RNA primer
        
        10 nucleotides from 5' end
        
        3'-5' exonuclease
        
        Role: accuracy of DNA synthesis
        
        Removes mispaired nucleotides from 3' end
        
        Loc: DNA polymerase I
    - - Sources of damage
        
        Environmental
        
        Ionizing radiation (UV, chemicals)
        
        Leads to lesions in DNA
      - 3 activities = maintain fidelity of DNA replication
        
        Accurate selections of nucleotides
        
        Immediate proofreading
        
        Post-replicative mismatch repair
        
        Nucleotide excision repair
        
        Pathways
        
        Transcription-coupled= preferred
        
        Func: select to repair genes of greatest importance
        
        global genomic pathway
        
        Func: corrects DNA strands in the remainder of the genome
        
        General mechanism
        
        Removes bulky lesions
        
        pyrimidine dimers
        
        chemically altered nucleotides
        
        Process
        
        Recognize => nuclease cleavage => DNA pol = replaces => ligase
        
        Base excision repair
        
        General mechanism
        
        Removes altered nucleotide = distort double helix
        
        Process
        
        DNA glycosylases = cleaves base => endonucleases = cleaves backbone => DNA pol = insert nucleotide => DNA ligase = seals
        
        Mismatch repair
        
        General mechanism
        
        Replace nucleotide = escape proofreading of DNA pol
        
        Process
        
        Recognize => recruit MMR proteins => DNA pol = resynthesize DNA sequence
        
        Chracteristics
        
        Bacteria: methylated adenine bases
        
        Eukaryotes: likely methylation-independent
        
        Double strand break repair
        
        Source
        
        Ionizing radiation
        
        Process
        
        Nonhomologous end joining
        
        Ku proteins = bind to broken ends => rejoins + mediated by DNA-dependent protein kinase catalytic subunit => DNA ligase = seal
    - - Def: noncoding sequences (nonprotein)
      - Func: ensure cell not lose genetic information if DNA shortens during replciation
      - Players
        
        Telomerase: adding repeats to telomere
        
        Composed: RNA& protein
        
        Telomere capping protein
        
        Protect the end from degradation
- - - - Genes
        
        Characteristics
        
        Undergo replication => 2 copies to each daughter cell
        
        Consist of DNA => functional products
        
        Def: heredity units
      - Double Helix
        
        Structures:
        
        Nucleotide
        
        Chargaff's rules
        
        A = T & C=G
        
        Structures
        
        Nitrogenous base = project out & Stacked themselves
        
        CUT the Pye: C & T (U of RNA) = pyrimidine
        
        1 more item...
        
        Pur As Gold = A & G = purines
        
        1 more item...
        
        sugar + phosphates = 3,5 phosphodiester bonds
        
        Minor groove
        
        Major groove
        
        Antiparallel orientation
        
        Synthesize 5'-3'
        
        Complementary strands
        
        Can separate for replication
        
        Developed: Watson & Crick
        
        Fr X-ray diffraction data of Rosalind Franklin
  - - - Eukaryotic model
        
        DNA => histones + DNA = nucleosomes => chromatin fibers => looped domains=> chromosomal scaffold => chromatin
      - Types
        
        Heterochromatin: compacted = no transcription
        
        Facultative heterochromatin
        
        can be converted to euchromatin & vice versa
        
        Constitutive heterochromatin
        
        Structural functions
        
        Ex: centromeres & telomeres
        
        Euchromatin: diffuse- transcription
    - - Positively charged
        
        Attract negatively charged DNA
        
        lysine & arginine content