MBIO - Lecture 10

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MBIO - Lecture 10
2011-03-04 12:12:34

the end of recombination
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  1. V(D)J Recombinaton
    V=variable region
    J=joining region
    • A: starts in the germ line
    • B: B cell DNA transcribed into Transcribed RNA then RNA splicing splices into Spliced mRNA which is then translated into a light chain protein
    • C: heavy chain protein
  2. Recombinaton "signal sequences"
    • 2 types of signal secuences
    • one has a 12bp spacer (surrounded by a 7mer and a 9mer)
    • second has a 23bp spacer (surrounded by a 7mer and a 9mer)
    • A: recombination signal sequences
    • B: single strand cleavage
    • C: herapin formation
    • D: herapin opening fusion conde of segments-->further recombination
    • D2: single joint formation-->DNA non homologous end joining proteins--> discarded

    rag1 and rag 2 bind to the signal sequences to for a hair pin loop
  3. DNA damage and repair
    • extrinsic damage: ultraviolet radiation, drugs, (ROS), (IR)
    • intrinsic damage: VDJ recombination, Class switching recombination (CSR), Somatic hyper mutation (SHM)
    • Other damage: telomere shortening, aging
    • Sensing: variety of sensing proteins
    • Signal transduction:
    • Outcome: Senesence(P53), Apoptosis(P53), transcriptional response, cell cycle arrest, DNA repair
  4. DNA Damage in the immune system
    • Bone Marrow:
    • Blymphocyte development: VDJ recombination, proliferation, ROS, telomere shortening
    • Hemapoptoetic stem cells: selfrenewal, proliferation, ROS, telomere shortening
    • Thymus:
    • T lymphocyte developement: VDJ recombination proliferation, ROS, telomere shortening
    • Secondary Lymphoid Organs:
    • B lymphocytes:CSR, SHM, Clonal expansion, ROS, Telomere shortening
    • T lymphocytes: endegenous proliferation and clonal expansion, ROS, telomere shortening
  5. Component defects in V(D)J recombinaton
  6. Non Homologous End Joining (NHEJ)
  7. Mutatons affectng the immune system and DNA repair
    • hypomorphic: loss of most function but retains some residual function (like a null allele)
    • types of mutations:
    • Artemis
    • DNA-Lig 4
    • Cemunnos
  8. Good damaged goods
    • Deamination: activation induced deamination, switches thymine to uracil
    • damaging the dna can also lead to improperly placed bps which contribute to dna diversity
  9. Base"excision"pathway
    in the CSR pathway: activation induced deaminase

    Generatng mutatons to enhance diversity in the immune system
  10. Generatng mutatons to enhance diversity in the immune system
  11. Translesion"DNA"synthesis"
    translesion proteins and enzymes have less accuracy in putting bps thus contributing to dna diversity
  12. Somatic hyper mutations