Article ; Online: Coupling of V(D)J recombination to the cell cycle suppresses genomic instability and lymphoid tumorigenesis.
2011 Volume 34, Issue 2, Page(s) 163–174
Abstract: V(D)J gene segment recombination is linked to the cell cycle by the periodic phosphorylation and ... the periodic destruction of RAG-2 and lymphoid tumorigenesis. We infer that cell cycle control of the V(D)J ...
| Abstract | V(D)J gene segment recombination is linked to the cell cycle by the periodic phosphorylation and destruction of the RAG-2 protein at the G1-to-S cell cycle transition. To examine the function of this coupling, we constructed mice in which the phosphorylation site at threonine 490 of RAG-2 was mutated to alanine. The RAG-2(T490A) mutation uncoupled DNA cleavage from cell cycle and promoted aberrant recombination. Similar aberrant recombination products were observed in mice deficient in the Skp2 ubiquitin ligase subunit, which is required for periodic destruction of RAG-2. On a p53-deficient background, the RAG-2(T490A) mutation induced lymphoid malignancies characterized by clonal chromosomal translocations involving antigen receptor genes. Taken together, these observations provide a direct link between the periodic destruction of RAG-2 and lymphoid tumorigenesis. We infer that cell cycle control of the V(D)J recombinase limits the potential genomic damage that could otherwise result from RAG-mediated DNA cleavage. |
|---|---|
| MeSH term(s) | Amino Acid Substitution ; Animals ; Base Sequence ; Cell Cycle ; DNA Breaks, Double-Stranded ; DNA Repair ; DNA-Binding Proteins/deficiency ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/physiology ; Female ; Gene Knock-In Techniques ; Gene Rearrangement ; Genes, p53 ; Genomic Instability ; Lymphoma, Non-Hodgkin/genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Phosphorylation ; Protein Processing, Post-Translational ; Receptors, Antigen, T-Cell/genetics ; S-Phase Kinase-Associated Proteins/genetics ; Specific Pathogen-Free Organisms ; T-Lymphocytes/metabolism ; Translocation, Genetic |
| Chemical Substances | DNA-Binding Proteins ; Rag2 protein, mouse ; Receptors, Antigen, T-Cell ; S-Phase Kinase-Associated Proteins |
| Language | English |
| Publishing date | 2011-02-22 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 1217235-2 |
| ISSN | 1097-4180 ; 1074-7613 |
| ISSN (online) | 1097-4180 |
| ISSN | 1074-7613 |
| DOI | 10.1016/j.immuni.2011.02.003 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 4227: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG) |
|||
| Zs.MG 69: Show issues |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.