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

• DOI: 10.1371/journal.pgen.1005645
• Publication Date: 2015-11-06T19:01:04Z
• Authors: Jana Prochazkova; Shinya Sakaguchi; Michel Owusu; Abdelghani Mazouzi; Marc Wiedner; Georgia Velimezi; Martin Moder; Gleb Turchinovich; Anastasiya Hladik; Elisabeth Gurnhofer; Adrian Hayday; Axel Behrens; Sylvia Knapp; Lukas Kenner; Wilfried Ellmeier; Joanna I. Loizou
• Keywords: Nijmegen breakage syndrome; Proinflammatory cytokine

Proper development of the immune system is an intricate process dependent on many factors, including intact DNA damage response. The double-strand break signaling kinase ATM and its cofactor NBS1 are required during T cell for maintenance genomic stability. role a second cofactor, ATMIN (also known as ASCIZ) in cells much less clear, whether function synergy unknown. Here, we investigate roles NBS1, either alone or combination, using murine models. We show loss led to developmental block at double-positive stage development, well reduced TCRα recombination, that was unexpectedly neither exacerbated nor alleviated by concomitant ATMIN. In contrast, both enhanced drove spontaneous peripheral hyperactivation, proliferation excessive production proinflammatory cytokines chemokines, leading highly inflammatory environment. Intriguingly, disease causing were largely proficient NBS1. vivo this resulted severe intestinal inflammation, colitis premature death. Our findings reveal novel model bowel phenotype occurs upon combined repair cofactors