Publication Date:
2006-12-16
Description:
Antibody class switching in activated B cells uses class switch recombination (CSR), which joins activation-induced cytidine deaminase (AID)-dependent double-strand breaks (DSBs) within two large immunoglobulin heavy chain (IgH) locus switch (S) regions that lie up to 200 kilobases apart. To test postulated roles of S regions and AID in CSR, we generated mutant B cells in which donor Smu and accepter Sgamma1 regions were replaced with yeast I-SceI endonuclease sites. We found that site-specific I-SceI DSBs mediate recombinational IgH locus class switching from IgM to IgG1 without S regions or AID. We propose that CSR evolved to exploit a general DNA repair process that promotes joining of widely separated DSBs within a chromosome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zarrin, Ali A -- Del Vecchio, Catherine -- Tseng, Eva -- Gleason, Megan -- Zarin, Payam -- Tian, Ming -- Alt, Frederick W -- 2P01AI031541-15/AI/NIAID NIH HHS/ -- P01CA092625-05/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2007 Jan 19;315(5810):377-81. Epub 2006 Dec 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Children's Hospital, CBR Institute for Biomedical Research, and Department of Genetics, Harvard University Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17170253" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
B-Lymphocytes/*immunology
;
Base Sequence
;
Cell Line
;
Cytidine Deaminase/*metabolism
;
*DNA Breaks, Double-Stranded
;
DNA Repair
;
Deoxyribonucleases, Type II Site-Specific/genetics/*metabolism
;
Embryonic Stem Cells
;
Gene Targeting
;
Genes, Immunoglobulin Heavy Chain
;
Hybridomas
;
*Immunoglobulin Class Switching
;
Immunoglobulin G/biosynthesis/genetics
;
Immunoglobulin M/biosynthesis/genetics
;
*Immunoglobulin Switch Region
;
Lymphocyte Activation
;
Mice
;
Mice, Inbred C57BL
;
Molecular Sequence Data
;
Mutation
;
Recombination, Genetic
;
Saccharomyces cerevisiae/enzymology
;
Saccharomyces cerevisiae Proteins
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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