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Review
, 10 (12), 1928-35

Unique and Redundant Functions of ATM and DNA-PKcs During V(D)J Recombination

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Review

Unique and Redundant Functions of ATM and DNA-PKcs During V(D)J Recombination

Eric J Gapud et al. Cell Cycle.

Abstract

Lymphocyte antigen receptor genes are assembled through the process of V(D)J recombination, during which pairwise DNA cleavage of gene segments results in the formation of four DNA ends that are resolved into a coding joint and a signal joint. The joining of these DNA ends occurs in G1-phase lymphocytes and is mediated by the non-homologous end-joining (NHEJ) pathway of DNA double-strand break (DSB) repair. The ataxia telangiectasia mutated (ATM) and the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), two related kinases, both function in the repair of DNA breaks generated during antigen receptor gene assembly. Although these proteins have unique functions during coding joint formation, their activities in signal joint formation, if any, have been less clear. However, two recent studies demonstrated that ATM and DNA-PKcs have overlapping activities important for signal joint formation. Here, we discuss the unique and shared activities of the ATM and DNA-PKcs kinases during V(D)J recombination, a process that is essential for lymphocyte development and the diversification of antigen receptors.

Figures

Figure 1
Figure 1
Models for overlapping activities of ATM and DNA-PKcs during V(D)J recombination: (A) ATM and DNA-PKcs may phoshorylate factors that are directly involved in signal joint formation or may phosphorylate proteins that indirectly promote the activity of joining factors. (B) ATM and DNA-PKcs may phoshorylate proteins that directly inhibit ligation, leading to their eviction from the DNA ends, or may phosphorylate proteins that actively evict these inhibitory proteins. (C) ATM and DNA-PKcs may directly phosphorylate histones in a way that makes signal end-associated chromatin accessible or may phosphorylate proteins that actively modify chromatin structure at RAG DSBs.

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