A regulatory role for the cohesin loader NIPBL in nonhomologous end joining during immunoglobulin class switch recombination.

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State: Public
Version: author
Serval ID
serval:BIB_D9ED1016C1ED
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A regulatory role for the cohesin loader NIPBL in nonhomologous end joining during immunoglobulin class switch recombination.
Journal
Journal of Experimental Medicine
Author(s)
Enervald E., Du L., Visnes T., Björkman A., Lindgren E., Wincent J., Borck G., Colleaux L., Cormier-Daire V., van Gent D.C., Pie J., Puisac B., de Miranda N.F., Kracker S., Hammarström L., de Villartay J.P., Durandy A., Schoumans J., Ström L., Pan-Hammarström Q.
ISSN
1540-9538 (Electronic)
ISSN-L
0022-1007
Publication state
Published
Issued date
2013
Volume
210
Number
12
Pages
2503-2513
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish. pdf type; Brief Definitive Report
Abstract
DNA double strand breaks (DSBs) are mainly repaired via homologous recombination (HR) or nonhomologous end joining (NHEJ). These breaks pose severe threats to genome integrity but can also be necessary intermediates of normal cellular processes such as immunoglobulin class switch recombination (CSR). During CSR, DSBs are produced in the G1 phase of the cell cycle and are repaired by the classical NHEJ machinery. By studying B lymphocytes derived from patients with Cornelia de Lange Syndrome, we observed a strong correlation between heterozygous loss-of-function mutations in the gene encoding the cohesin loading protein NIPBL and a shift toward the use of an alternative, microhomology-based end joining during CSR. Furthermore, the early recruitment of 53BP1 to DSBs was reduced in the NIPBL-deficient patient cells. Association of NIPBL deficiency and impaired NHEJ was also observed in a plasmid-based end-joining assay and a yeast model system. Our results suggest that NIPBL plays an important and evolutionarily conserved role in NHEJ, in addition to its canonical function in sister chromatid cohesion and its recently suggested function in HR.
Pubmed
Web of science
Open Access
Yes
Create date
22/12/2013 17:03
Last modification date
20/08/2019 15:59
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