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PMID: 11717442 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 98 ·No. 24 ·2001-11-20 ·Pages 13860-5

Chen X, Kinoshita K, Honjo T

Abstract

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.

MeSH Terms
Animals Base Sequence Cell Line Chromosome Inversion DNA, Complementary Gene Deletion Gene Duplication Genes, Immunoglobulin Humans Immunoglobulin Class Switching/genetics Immunoglobulin Switch Region/genetics Immunoglobulin mu-Chains/genetics Mice Molecular Sequence Data Nucleic Acid Conformation Point Mutation Recombination, Genetic Sequence Analysis, DNA
Chemicals
DNA, Complementary Immunoglobulin mu-Chains
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Chen X
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku Kyoto 606-8501, Japan.
Kinoshita K
Honjo T
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.241524898
Published
2001-11-20
Pages
13860-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC61132
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.241524898 PMC Full Text View journal details
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