Variable deletion and duplication at recombination junction ends: Implication for staggered double-strand cleavage in class-switch recombination

被引:66
作者
Chen, XC [1 ]
Kinoshita, K [1 ]
Honjo, T [1 ]
机构
[1] Kyoto Univ, Grad Sch Med, Dept Med Chem, Sakyo Ku, Kyoto 6068501, Japan
关键词
D O I
10.1073/pnas.241524898
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页码:13860 / 13865
页数:6
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