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Publication : DNA-dependent protein kinase activity is not required for immunoglobulin class switching.

First Author  Bosma GC Year  2002
Journal  J Exp Med Volume  196
Issue  11 Pages  1483-95
PubMed ID  12461083 Mgi Jnum  J:118010
Mgi Id  MGI:3698350 Doi  10.1084/jem.20001871
Citation  Bosma GC, et al. (2002) DNA-dependent protein kinase activity is not required for immunoglobulin class switching. J Exp Med 196(11):1483-95
abstractText  Class switch recombination (CSR), similar to V(D)J recombination, is thought to involve DNA double strand breaks and repair by the nonhomologous end-joining pathway. A key component of this pathway is DNA-dependent protein kinase (DNA-PK), consisting of a catalytic subunit (DNA-PKcs) and a DNA-binding heterodimer (Ku70/80). To test whether DNA-PKcs activity is essential for CSR, we examined whether IgM(+) B cells from scid mice with site-directed H and L chain transgenes were able to undergo CSR. Although B cells from these mice were shown to lack DNA-PKcs activity, they were able to switch from IgM to IgG or IgA with close to the same efficiency as B cells from control transgenic and nontransgenic scid/+ mice, heterozygous for the scid mutation. We conclude that CSR, unlike V(D)J recombination, can readily occur in the absence of DNA-PKcs activity. We suggest nonhomologous end joining may not be the (primary or only) mechanism used to repair DNA breaks during CSR.
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