ArticleThe Journal of biological chemistry2012
A dual interaction between the DNA damage response protein MDC1 and the RAG1 subunit of the V(D)J recombinase.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Dynamic chromatin tethering of MDC1 regulates genome stability.Nucleic acids research · 2026Article
- The PST repeat region of MDC1 is a tunable multivalent chromatin tethering domain.bioRxiv : the preprint server for biology · 2025Article
- RORγt up-regulates RAG gene expression in DP thymocytes to expand theScience immunology · 2024Article
- Nuclease-independent functions of RAG1 direct distinct DNA damage responses in B cells.EMBO reports · 2023Article
- MiRAGDB: A Knowledgebase of RAG Regulators.Frontiers in immunology · 2022Article
- The RAG1 N-terminal region regulates the efficiency and pathways of synapsis for V(D)J recombination.The Journal of experimental medicine · 2021Article
- The CRL4VPRBP(DCAF1) E3 ubiquitin ligase directs constitutive RAG1 degradation in a non-lymphoid cell line.PloS one · 2021Article
- Intra-Vκ Cluster Recombination Shapes the Ig Kappa Locus Repertoire.Cell reports · 2019Article
- VprBP (DCAF1) Regulates RAG1 Expression Independently of Dicer by Mediating RAG1 Degradation.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- New insights into the evolutionary origins of the recombination-activating gene proteins and V(D)J recombination.The FEBS journal · 2017Review
- Immature Lymphocytes InhibitJournal of immunology (Baltimore, Md. : 1950) · 2017Article
- Riches in RAGs: Revealing the V(D)J Recombinase through High-Resolution Structures.Trends in biochemical sciences · 2017Review
- Recruitment of RAG1 and RAG2 to Chromatinized DNA during V(D)J Recombination.Molecular and cellular biology · 2015Article
- Article
- Mapping and Quantitation of the Interaction between the Recombination Activating Gene Proteins RAG1 and RAG2.The Journal of biological chemistry · 2015Article
- Spatio-temporal regulation of RAG2 following genotoxic stress.DNA repair · 2015Article
- Mdb1, a fission yeast homolog of human MDC1, modulates DNA damage response and mitotic spindle function.PloS one · 2014Article
- Peripheral subnuclear positioning suppresses Tcrb recombination and segregates Tcrb alleles from RAG2.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- The ataxia telangiectasia mutated kinase controls Igκ allelic exclusion by inhibiting secondary Vκ-to-Jκ rearrangements.The Journal of experimental medicine · 2013Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The first step in V(D)J recombination is the formation of specific DNA double-strand breaks (DSBs) by the RAG1 and RAG2 proteins, which form the RAG recombinase. DSBs activate a complex network of proteins termed the DNA damage response (DDR). A key early event in the DDR is the phosphorylation of histone H2AX around DSBs, which forms a binding site for the tandem BRCA1 C-terminal (tBRCT) domain of MDC1. This event is required for subsequent signal amplification and recruitment of additional DDR proteins to the break site. RAG1 bears a histone H2AX-like motif at its C terminus (R1Ct), making it a putative MDC1-binding protein. In this work we show that the tBRCT domain of MDC1 binds the R1Ct motif of RAG1. Surprisingly, we also observed a second binding interface between the two proteins that involves the Proline-Serine-Threonine rich (PST) repeats of MDC1 and the N-terminal non-core region of RAG1 (R1Nt). The repeats-R1Nt interaction is constitutive, whereas the tBRCT-R1Ct interaction likely requires phosphorylation of the R1Ct motif of RAG1. As the C terminus of RAG1 has been implicated in inhibition of RAG activity, we propose a model in which phosphorylation of the R1Ct motif of RAG1 functions as a self-initiated regulatory signal.
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