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Cernunnos influence...
Cernunnos influences human immunoglobulin class switch recombination and may be associated with B cell lymphomagenesis
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- Du, Likun (author)
- Karolinska Institutet
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Peng, Roujun (author)
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- Björkman, Andrea (author)
- Karolinska Institutet
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- Filipe de Miranda, Noel (author)
- Karolinska Institutet
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Rosner, Cornelia (author)
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Kotnis, Ashwin (author)
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- Berglund, Mattias (author)
- Uppsala universitet,Enheten för onkologi
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Liu, Chonghai (author)
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- Rosenquist, Richard (author)
- Uppsala universitet,Hematologi och immunologi,Rosenquist Brandell
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- Enblad, Gunilla (author)
- Uppsala universitet,Enheten för onkologi
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- Sundström, Christer (author)
- Uppsala universitet,Molekylär och morfologisk patologi
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- Hojjat-Farsangi, Mohammad (author)
- Karolinska Institutet
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Rabbani, Hodjattallah (author)
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Teixeira, Manuel R (author)
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Revy, Patrick (author)
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Durandy, Anne (author)
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Zeng, Yixin (author)
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Gennery, Andrew R (author)
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de Villartay, Jean-Pierre (author)
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- Pan-Hammarström, Qiang (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2012-02-06
- 2012
- English.
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In: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 209:2, s. 291-305
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https://urn.kb.se/re...
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Abstract
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- Cernunnos is involved in the nonhomologous end-joining (NHEJ) process during DNA double-strand break (DSB) repair. Here, we studied immunoglobulin (Ig) class switch recombination (CSR), a physiological process which relies on proper repair of the DSBs, in B cells from Cernunnos-deficient patients. The pattern of in vivo generated CSR junctions is altered in these cells, with unusually long microhomologies and a lack of direct end-joining. The CSR junctions from Cernunnos-deficient patients largely resemble those from patients lacking DNA ligase IV, Artemis, or ATM, suggesting that these factors are involved in the same end-joining pathway during CSR. By screening 269 mature B cell lymphoma biopsies, we also identified a somatic missense Cernunnos mutation in a diffuse large B cell lymphoma sample. This mutation has a dominant-negative effect on joining of a subset of DNA ends in an in vitro NHEJ assay. Translocations involving both Ig heavy chain loci and clonal-like, dynamic IgA switching activities were observed in this tumor. Collectively, our results suggest a link between defects in the Cernunnos-dependent NHEJ pathway and aberrant CSR or switch translocations during the development of B cell malignancies.
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- art (subject category)
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- By the author/editor
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Du, Likun
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Peng, Roujun
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Björkman, Andrea
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Filipe de Mirand ...
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Rosner, Cornelia
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Kotnis, Ashwin
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show more...
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Berglund, Mattia ...
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Liu, Chonghai
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Rosenquist, Rich ...
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Enblad, Gunilla
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Sundström, Chris ...
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Hojjat-Farsangi, ...
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Rabbani, Hodjatt ...
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Teixeira, Manuel ...
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Revy, Patrick
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Durandy, Anne
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Zeng, Yixin
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Gennery, Andrew ...
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de Villartay, Je ...
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Pan-Hammarström, ...
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Journal of Exper ...
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Uppsala University
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Karolinska Institutet