The beyond 12/23 restriction is imposed at the nicking and pairing steps of DNA cleavage during V(D)J recombination.

The beyond 12/23 restriction is imposed at the nicking and pairing steps of DNA cleavage during V(D)J recombination. Research Abstract Details 

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The beyond 12/23 restriction is imposed at the nicking and pairing steps of DNA cleavage during V(D)J recombination. Abstract Text:

Anna H Drejer-Teel,Sebastian D Fugmann,David G Schatz,

The beyond 12/23 (B12/23) rule ensures inclusion of a Dbeta gene segment in the assembled T-cell receptor (TCR) beta variable region exon and is manifest by a failure of direct Vbeta-to-Jbeta gene segment joining. The restriction is enforced during the DNA cleavage step of V(D)J recombination by the recombination-activating gene 1 and 2 (RAG1/2) proteins and the recombination signal sequences (RSSs) flanking the TCRbeta gene segments. Nothing is known about the step(s) at which DNA cleavage is defective or how TCRbeta locus sequences contribute to these defects. To address this, we examined the steps of DNA cleavage by the RAG proteins using TCRbeta locus V, D, and J RSS oligonucleotide substrates. The results demonstrate that the B12/23 rule is enforced through slow nicking of Jbeta substrates and to some extent through poor synapsis of Vbeta and Jbeta substrates. Nicking is controlled largely by the coding flank and, unexpectedly, the RSS spacer, while synapsis is controlled primarily by the RSS nonamer. The results demonstrate that different Jbeta substrates are crippled at different steps of cleavage by distinct combinations of defects in the various DNA elements and strongly suggest that the DNA nicking step of V(D)J recombination can be rate limiting in vivo.

The beyond 12/23 restriction is imposed at the nicking and pairing steps of DNA cleavage during V(D)J recombination. Publishing Authors By Initials

AH Drejer-Teel,SD Fugmann,DG Schatz,

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: substrate specificity research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: substrate specificity research

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The beyond 12/23 restriction is imposed at the nicking and pairing steps of DNA cleavage during V(D)J recombination. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular and cellular biology

VOLUME: 27

Page Numbers: 6288-99

Journal Abbreviation: Mol. Cell. Biol.

ISSN: 0270-7306

DAY: 16

MONTH: 07

YEAR: 2007

The beyond 12/23 restriction is imposed at the nicking and pairing steps of DNA cleavage during V(D)J recombination. Information

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LANGUAGE: eng

NlmUniqueID: 8109087

The beyond 12/23 restriction is imposed at the nicking and pairing steps of DNA cleavage during V(D)J recombination. Keywords Mesh Terms:

KEYWORDS: Substrate Specificity

MESH TERMS: metabolism

Chemical & Substance for Abstract: The beyond 12/23 restriction is imposed at the nicking and pairing steps of DNA cleavage during V(D)J recombination. Information

Substance Name: Glutathione Transferase

Registry Number: EC 2.5.1.18

Grant and Affiliation Information for The beyond 12/23 restriction is imposed at the nicking and pairing steps of DNA cleavage during V(D)J recombination.

AFFILIATION: Department of Genetics, Yale University School of Medicine, 330 Cedar St., New Haven, Connecticut 06510, USA.

Country: United States

AGENCY: United States NIAID

GRANT: AI32524

ACRONYM: AI

MEDLINETA: Mol Cell Biol

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