Recombination-activating gene proteins

More regulation, please

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Developing B and T cells assemble gene segments in order to create the variable regions of immunoglobulin and T-cell receptors required by our adaptive immune response. The chemistry of this recombination pathway requires a specific nuclease and a more general repair pathway for double-strand breaks. A complex of the recombination-activating gene 1 (RAG1) and RAG2 proteins provides the nuclease activity. In fact, RAG1 and RAG2 probably coordinate many steps involving the coding and signaling DNA sequences. Studies using deletion and truncation mutants of the RAG proteins demonstrate that each of these contain a functional core region, representing about two-thirds of the polypeptides. While the core regions are sufficient to catalyze recombination in test systems, the full-length proteins seem to show more complicated behaviors in vivo. A plausible explanation is that regions outside the core help in the proper regulation of recombination. The non-core region of RAG1 has been found to contain a ubiquitin ligase. Regulatory functions may contribute to autoregulation of the proteins involved, fidelity of the reaction, protection of the cell from translocations, coordination of recombination with the cell cycle, and possibly modification of the chromatin structure of target DNA.

Original languageEnglish (US)
Pages (from-to)83-89
Number of pages7
JournalImmunological Reviews
Volume200
DOIs
StatePublished - Aug 2004

Fingerprint

RAG-1 Genes
Genetic Recombination
Proteins
Immunoglobulin Variable Region
Cytoprotection
Adaptive Immunity
Mutant Proteins
Ligases
Ubiquitin
T-Cell Antigen Receptor
Chromatin
Cell Cycle
Homeostasis
B-Lymphocytes
T-Lymphocytes
Peptides
DNA
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Recombination-activating gene proteins : More regulation, please. / Sadofsky, Moshe J.

In: Immunological Reviews, Vol. 200, 08.2004, p. 83-89.

Research output: Contribution to journalArticle

@article{4693cd72d19846bebdaac885f419c22e,
title = "Recombination-activating gene proteins: More regulation, please",
abstract = "Developing B and T cells assemble gene segments in order to create the variable regions of immunoglobulin and T-cell receptors required by our adaptive immune response. The chemistry of this recombination pathway requires a specific nuclease and a more general repair pathway for double-strand breaks. A complex of the recombination-activating gene 1 (RAG1) and RAG2 proteins provides the nuclease activity. In fact, RAG1 and RAG2 probably coordinate many steps involving the coding and signaling DNA sequences. Studies using deletion and truncation mutants of the RAG proteins demonstrate that each of these contain a functional core region, representing about two-thirds of the polypeptides. While the core regions are sufficient to catalyze recombination in test systems, the full-length proteins seem to show more complicated behaviors in vivo. A plausible explanation is that regions outside the core help in the proper regulation of recombination. The non-core region of RAG1 has been found to contain a ubiquitin ligase. Regulatory functions may contribute to autoregulation of the proteins involved, fidelity of the reaction, protection of the cell from translocations, coordination of recombination with the cell cycle, and possibly modification of the chromatin structure of target DNA.",
author = "Sadofsky, {Moshe J.}",
year = "2004",
month = "8",
doi = "10.1111/j.0105-2896.2004.00164.x",
language = "English (US)",
volume = "200",
pages = "83--89",
journal = "Immunological Reviews",
issn = "0105-2896",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Recombination-activating gene proteins

T2 - More regulation, please

AU - Sadofsky, Moshe J.

PY - 2004/8

Y1 - 2004/8

N2 - Developing B and T cells assemble gene segments in order to create the variable regions of immunoglobulin and T-cell receptors required by our adaptive immune response. The chemistry of this recombination pathway requires a specific nuclease and a more general repair pathway for double-strand breaks. A complex of the recombination-activating gene 1 (RAG1) and RAG2 proteins provides the nuclease activity. In fact, RAG1 and RAG2 probably coordinate many steps involving the coding and signaling DNA sequences. Studies using deletion and truncation mutants of the RAG proteins demonstrate that each of these contain a functional core region, representing about two-thirds of the polypeptides. While the core regions are sufficient to catalyze recombination in test systems, the full-length proteins seem to show more complicated behaviors in vivo. A plausible explanation is that regions outside the core help in the proper regulation of recombination. The non-core region of RAG1 has been found to contain a ubiquitin ligase. Regulatory functions may contribute to autoregulation of the proteins involved, fidelity of the reaction, protection of the cell from translocations, coordination of recombination with the cell cycle, and possibly modification of the chromatin structure of target DNA.

AB - Developing B and T cells assemble gene segments in order to create the variable regions of immunoglobulin and T-cell receptors required by our adaptive immune response. The chemistry of this recombination pathway requires a specific nuclease and a more general repair pathway for double-strand breaks. A complex of the recombination-activating gene 1 (RAG1) and RAG2 proteins provides the nuclease activity. In fact, RAG1 and RAG2 probably coordinate many steps involving the coding and signaling DNA sequences. Studies using deletion and truncation mutants of the RAG proteins demonstrate that each of these contain a functional core region, representing about two-thirds of the polypeptides. While the core regions are sufficient to catalyze recombination in test systems, the full-length proteins seem to show more complicated behaviors in vivo. A plausible explanation is that regions outside the core help in the proper regulation of recombination. The non-core region of RAG1 has been found to contain a ubiquitin ligase. Regulatory functions may contribute to autoregulation of the proteins involved, fidelity of the reaction, protection of the cell from translocations, coordination of recombination with the cell cycle, and possibly modification of the chromatin structure of target DNA.

UR - http://www.scopus.com/inward/record.url?scp=3242886494&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3242886494&partnerID=8YFLogxK

U2 - 10.1111/j.0105-2896.2004.00164.x

DO - 10.1111/j.0105-2896.2004.00164.x

M3 - Article

VL - 200

SP - 83

EP - 89

JO - Immunological Reviews

JF - Immunological Reviews

SN - 0105-2896

ER -