V(D)J recombination: Mechanisms of initiation

David G. Schatz, Patrick Swanson

Research output: Contribution to journalArticle

230 Citations (Scopus)

Abstract

V(D)J recombination assembles immunoglobulin and T cell receptor genes during lymphocyte development through a series of carefully orchestrated DNA breakage and rejoining events. DNA cleavage requires a series of protein-DNA complexes containing the RAG1 and RAG2 proteins and recombination signals that flank the recombining gene segments. In this review, we discuss recent advances in our understanding of the function and domain organization of the RAG proteins, the composition and structure of RAG-DNA complexes, and the pathways that lead to the formation of these complexes. We also consider the functional significance of RAG-mediated histone recognition and ubiquitin ligase activities, and the role played by RAG in ensuring proper repair of DNA breaks made during V(D)J recombination. Finally, we propose a model for the formation of RAG-DNA complexes that involves anchoring of RAG1 at the recombination signal nonamer and RAG2-dependent surveillance of adjoining DNA for suitable spacer and heptamer sequences.

Original languageEnglish
Pages (from-to)167-202
Number of pages36
JournalAnnual Review of Genetics
Volume45
DOIs
StatePublished - 2011

Fingerprint

V(D)J Recombination
DNA
Genetic Recombination
T-Cell Receptor Genes
DNA Cleavage
Proteins
Intergenic DNA
DNA Breaks
Ligases
Ubiquitin
Histones
Immunoglobulins
Lymphocytes
Genes

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

V(D)J recombination : Mechanisms of initiation. / Schatz, David G.; Swanson, Patrick.

In: Annual Review of Genetics, Vol. 45, 2011, p. 167-202.

Research output: Contribution to journalArticle

@article{5c77e757c2024d4687c6feb7b3909264,
title = "V(D)J recombination: Mechanisms of initiation",
abstract = "V(D)J recombination assembles immunoglobulin and T cell receptor genes during lymphocyte development through a series of carefully orchestrated DNA breakage and rejoining events. DNA cleavage requires a series of protein-DNA complexes containing the RAG1 and RAG2 proteins and recombination signals that flank the recombining gene segments. In this review, we discuss recent advances in our understanding of the function and domain organization of the RAG proteins, the composition and structure of RAG-DNA complexes, and the pathways that lead to the formation of these complexes. We also consider the functional significance of RAG-mediated histone recognition and ubiquitin ligase activities, and the role played by RAG in ensuring proper repair of DNA breaks made during V(D)J recombination. Finally, we propose a model for the formation of RAG-DNA complexes that involves anchoring of RAG1 at the recombination signal nonamer and RAG2-dependent surveillance of adjoining DNA for suitable spacer and heptamer sequences.",
author = "Schatz, {David G.} and Patrick Swanson",
year = "2011",
doi = "10.1146/annurev-genet-110410-132552",
language = "English",
volume = "45",
pages = "167--202",
journal = "Annual Review of Genetics",
issn = "0066-4197",
publisher = "Annual Reviews Inc.",

}

TY - JOUR

T1 - V(D)J recombination

T2 - Mechanisms of initiation

AU - Schatz, David G.

AU - Swanson, Patrick

PY - 2011

Y1 - 2011

N2 - V(D)J recombination assembles immunoglobulin and T cell receptor genes during lymphocyte development through a series of carefully orchestrated DNA breakage and rejoining events. DNA cleavage requires a series of protein-DNA complexes containing the RAG1 and RAG2 proteins and recombination signals that flank the recombining gene segments. In this review, we discuss recent advances in our understanding of the function and domain organization of the RAG proteins, the composition and structure of RAG-DNA complexes, and the pathways that lead to the formation of these complexes. We also consider the functional significance of RAG-mediated histone recognition and ubiquitin ligase activities, and the role played by RAG in ensuring proper repair of DNA breaks made during V(D)J recombination. Finally, we propose a model for the formation of RAG-DNA complexes that involves anchoring of RAG1 at the recombination signal nonamer and RAG2-dependent surveillance of adjoining DNA for suitable spacer and heptamer sequences.

AB - V(D)J recombination assembles immunoglobulin and T cell receptor genes during lymphocyte development through a series of carefully orchestrated DNA breakage and rejoining events. DNA cleavage requires a series of protein-DNA complexes containing the RAG1 and RAG2 proteins and recombination signals that flank the recombining gene segments. In this review, we discuss recent advances in our understanding of the function and domain organization of the RAG proteins, the composition and structure of RAG-DNA complexes, and the pathways that lead to the formation of these complexes. We also consider the functional significance of RAG-mediated histone recognition and ubiquitin ligase activities, and the role played by RAG in ensuring proper repair of DNA breaks made during V(D)J recombination. Finally, we propose a model for the formation of RAG-DNA complexes that involves anchoring of RAG1 at the recombination signal nonamer and RAG2-dependent surveillance of adjoining DNA for suitable spacer and heptamer sequences.

UR - http://www.scopus.com/inward/record.url?scp=80355122714&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80355122714&partnerID=8YFLogxK

U2 - 10.1146/annurev-genet-110410-132552

DO - 10.1146/annurev-genet-110410-132552

M3 - Article

C2 - 21854230

AN - SCOPUS:80355122714

VL - 45

SP - 167

EP - 202

JO - Annual Review of Genetics

JF - Annual Review of Genetics

SN - 0066-4197

ER -