3.30.10.euk DNA replication.bb - DNA recombination 1....

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DNA recombination 1. Homologous recombination - meiotic recombination and mitotic recombinational repair 2. Site specific recombination - phase variation, viral integration and excision 3. Non-homologous recombination - transposition, immunoglobulin gene recombination (V(D)J recombination) Mechanism: 1 and 2 involve Holliday junction intermediates, not 3
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Antibody diversity is generated by programmed DNA rearrangement Generation of up to 1.5 x 10 7 possible IgG (immunoglobulin G) genes from separate gene segments in vertebrate genomes by specialized recombination Fig 5-23
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Immunoglobulin genes assemble by recombination Bone marrow stem cells Each B lymphocyte has a different combination of V-J-C Programmed DNA deletion Each B lymphocyte produces an IgG that has a unique antigen binding site The light chain can combine with any of 5000 heavy chains to produce an antibody molecule 95 a.a 12 aa 4 Imprecise, variability 2.5X
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The mechanism for the VJ gene segments of the human IgG kappa light chain involves double strand breaks that is similar to several reaction steps in transposition. The genome contains ~300 different V segments, 4 different J segments, and 1C segment = 300 x 4 =1200 possible V-J combinations. RNA splicing process is imprecise, generates about 2.5 x 1200 = 3000 different V-J combinations. Heavy chains have more than 5000 possible combinations.
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This note was uploaded on 12/20/2011 for the course BIOLOGICAL 3310 taught by Professor Goldburg during the Spring '10 term at Cornell University (Engineering School).

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3.30.10.euk DNA replication.bb - DNA recombination 1....

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