DNA Repair Cofactors ATMIN and NBS1 Are Required to Suppress T Cell Activation

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Defects in DNA repair pathways can lead to pathogenesis within the immune system, an example of which is inflammatory bowel disease (IBD). Yet the underlying genetic causes of IBD are often unclear. The DNA repair kinase ATM is crucial for the proper development and function of the immune system. ATM is regulated in a stimulus dependent manner by its cofactors, ATMIN and NBS1. These cofactors compete for ATM binding and in doing so regulate ATM kinase activity. Whereas both ATM and NBS1 function in T cell development and in the maintenance of genomic stability within such cells, the role of ATMIN (and the contribution of ATMIN and NBS1) in T cell function is unknown. Here, we show that whereas NBS1 has distinct ATMIN-independent functions during VDJ recombination, loss of both cofactors resulted in exacerbated DNA damage, T cell hyperactivation, inflammation and an IBD phenotype. The pathology was driven by T cells largely proficient for both ATMIN and NBS1. These data demonstrate additive effects revealed upon loss of both ATMIN and NBS1, thus illustrating the importance of these two DNA repair cofactors in proper T cell development and function.

Vyšlo v časopise: DNA Repair Cofactors ATMIN and NBS1 Are Required to Suppress T Cell Activation. PLoS Genet 11(11): e32767. doi:10.1371/journal.pgen.1005645
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005645

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