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DNA-PKcs Is Involve...
DNA-PKcs Is Involved in Ig Class Switch Recombination in Human B Cells
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- Bjorkman, A (author)
- Karolinska Institutet
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Du, LK (author)
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Felgentreff, K (author)
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Rosner, C (author)
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Kamdar, RP (author)
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- Kokaraki, G (author)
- Karolinska Institutet
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Matsumoto, Y (author)
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Davies, EG (author)
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van der Burg, M (author)
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Notarangelo, LD (author)
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- Hammarstrom, L (author)
- Karolinska Institutet
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- Pan-Hammarstrom, Q (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2015-12-15
- 2015
- English.
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In: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 195:12, s. 5608-5615
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https://doi.org/10.4...
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Abstract
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- Nonhomologous end-joining (NHEJ) is one of the major DNA double-strand break repair pathways in mammalian cells and is required for both V(D)J recombination and class switch recombination (CSR), two Ig gene–diversification processes occurring during B cell development. DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) is a component of the classical NHEJ machinery and has a critical function during V(D)J recombination. However, its role in CSR has been controversial. In this study, we examined the pattern of recombination junctions from in vivo–switched B cells from two DNA-PKcs–deficient patients. One of them harbored mutations that did not affect DNA-PKcs kinase activity but caused impaired Artemis activation; the second patient had mutations resulting in diminished DNA-PKcs protein expression and kinase activity. These results were compared with those from DNA-PKcs–deficient mouse B cells. A shift toward the microhomology-based alternative end-joining at the recombination junctions was observed in both human and mouse B cells, suggesting that the classical NHEJ pathway is impaired during CSR when DNA-PKcs is defective. Furthermore, cells from the second patient showed additional or more severe alterations in CSR and/or NHEJ, which may suggest that DNA-PKcs and/or its kinase activity have additional, Artemis-independent functions during these processes.
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Bjorkman, A
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Du, LK
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Felgentreff, K
-
Rosner, C
-
Kamdar, RP
-
Kokaraki, G
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show more...
-
Matsumoto, Y
-
Davies, EG
-
van der Burg, M
-
Notarangelo, LD
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Hammarstrom, L
-
Pan-Hammarstrom, ...
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show less...
- Articles in the publication
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Journal of immun ...
- By the university
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Karolinska Institutet