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CtIP is essential for early B cell proliferation and development in mice

ABSTRACT: B cell development requires efficient proliferation and successful assembly and modifications of the immunoglobulin gene products. CtIP is an essential gene implicated in end-resection and DNA repair. Here we show that CtIP is essential for early B cell development, while dispensable in naïve B cells. CtIP loss is well-tolerated in G1 arrested B cells and during V(D)J recombination. But, in proliferating B cells, CtIP loss leads to a progressive cell death characterized by ATM hyper-activation, G2/M arrest, genomic instability, and 53BP1 nuclear body formation, indicating that the essential role of CtIP during proliferation underscores its stage-specific requirement in B cells. B cell proliferation requires phosphorylation of CtIP at T847 presumably by CDK, but not its interaction with CtBP, Rb, nor its nuclease activity. CtIP phosphorylation by ATM/ATR at T859 (T855 in mice) promotes end-resection in G1 arrested cells, but dispensable for B cell development and class switch recombination, suggesting distinct roles for T859 and T847 phosphorylation in B cell development.

ORGANISM(S): Mus musculus

PROVIDER: GSE129850 | GEO | 2019/05/12

REPOSITORIES: GEO

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