uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Cernunnos influences human immunoglobulin class switch recombination and may be associated with B cell lymphomagenesis
Show others and affiliations
2012 (English)In: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 209, no 2, 291-305 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2012. Vol. 209, no 2, 291-305 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-170963DOI: 10.1084/jem.20110325ISI: 000301943200010PubMedID: 22312109OAI: oai:DiVA.org:uu-170963DiVA: diva2:509951
Available from: 2012-03-14 Created: 2012-03-14 Last updated: 2012-04-23Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Berglund, MattiasRosenquist, RichardEnblad, GunillaSundström, Christer
By organisation
OncologyHematology and ImmunologyMolecular and Morphological Pathology
In the same journal
Journal of Experimental Medicine
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 285 hits
ReferencesLink to record
Permanent link

Direct link