PUBLICATION
RAG2 abolishes RAG1 aggregation to facilitate V(D)J recombination
- Authors
- Gan, T., Wang, Y., Liu, Y., Schatz, D.G., Hu, J.
- ID
- ZDB-PUB-211015-12
- Date
- 2021
- Source
- Cell Reports 37: 109824 (Journal)
- Registered Authors
- Keywords
- B lymphocytes, Protein aggregation, RAG complex, V(D)J recombination
- MeSH Terms
-
- Cell Line, Tumor
- Cell Nucleus Structures/genetics
- Cell Nucleus Structures/metabolism*
- DNA-Binding Proteins/genetics
- DNA-Binding Proteins/metabolism*
- G1 Phase*
- HEK293 Cells
- Homeodomain Proteins/genetics
- Homeodomain Proteins/metabolism*
- Humans
- Lymphocytes/metabolism*
- Nuclear Proteins/genetics
- Nuclear Proteins/metabolism*
- Protein Aggregates
- Species Specificity
- V(D)J Recombination*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 34644584 Full text @ Cell Rep.
Citation
Gan, T., Wang, Y., Liu, Y., Schatz, D.G., Hu, J. (2021) RAG2 abolishes RAG1 aggregation to facilitate V(D)J recombination. Cell Reports. 37:109824.
Abstract
RAG1 and RAG2 form a tetramer nuclease to initiate V(D)J recombination in developing T and B lymphocytes. The RAG1 protein evolves from a transposon ancestor and possesses nuclease activity that requires interaction with RAG2. Here, we show that the human RAG1 aggregates in the nucleus in the absence of RAG2, exhibiting an extremely low V(D)J recombination activity. In contrast, RAG2 does not aggregate by itself, but it interacts with RAG1 to disrupt RAG1 aggregates and thereby activate robust V(D)J recombination. Moreover, RAG2 from mouse and zebrafish could not disrupt the aggregation of human RAG1 as efficiently as human RAG2 did, indicating a species-specific regulatory mechanism for RAG1 by RAG2. Therefore, we propose that RAG2 coevolves with RAG1 to release inert RAG1 from aggregates and thereby activate V(D)J recombination to generate diverse antigen receptors in lymphocytes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping