Variable deletion and duplication at recombination junction ends: implication for staggered double-strand cleavage in class-switch recombination.
Immunoglobulin class-switch recombination (CSR) gives rise to looped-out circular DNA of a cleaved S segment, which is lost eventually after cell divisions. To understand the molecular mechanism of S region cleavage during CSR, we constructed artificial CSR substrates in which inversion-type CSR takes place to retain the cleaved S segment. Sequencing analyses of recombinant clones of these substrates revealed that varying degrees of deletions and duplications exist at CSR breakpoints, suggesting the involvement of staggered cleavage of the S region in CSR. In addition, mutations frequently found near junctions showed a similar profile of base replacement to Ig somatic hypermutation. These findings suggest that single-strand tails of staggered cleavage may be repaired by error-prone DNA synthesis.
Chen
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Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku Kyoto 606-8501, Japan.
Kinoshita
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K
Honjo
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T
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D007446:Chromosome Inversion; D018076:DNA, Complementary; D017353:Gene Deletion; D020440:Gene Duplication; D005803:Genes, Immunoglobulin; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D007134:Immunoglobulin Switch Region / Q000235:genetics*; D007148:Immunoglobulin mu-Chains / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D017354:Point Mutation; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA
D018076:DNA, Complementary; D007148:Immunoglobulin mu-Chains