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J Biol Chem, Vol. 275, Issue 12, 8341-8348, March 24, 2000
From the Howard Hughes Medical Institute, Section of Immunobiology,
Yale University School of Medicine,
New Haven, Connecticut 06520-8011
V(D)J recombination plays a prominent role in the
generation of the antigen receptor repertoires of B and T lymphocytes.
It is also likely to be involved in the formation of chromosomal translocations, some of which may result from interchromosomal recombination. We have investigated the potential of the V(D)J recombination machinery to perform intermolecular recombination between
two plasmids, either unlinked or linked by catenation. In either case,
recombination occurs in trans to yield signal and coding
joints, and the results do not support the existence of a mechanistic
block to the formation of coding joints in trans. Instead,
we observe that linearization of the substrate, which does not alter
the cis or trans status of the recombination
signals, causes a specific and dramatic reduction in coding joint
formation. This unexpected result leads us to propose a "release and
recapture" model for V(D)J recombination in which coding ends are
frequently released from the postcleavage complex and the efficiency of
coding joint formation is influenced by the efficiency with which such ends are recaptured by the complex. This implies the existence of
mechanisms, operative during recombination of chromosomal substrates, that act to prevent coding end release or to facilitate coding end recapture.
Intermolecular V(D)J Recombination*
and
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Postdoctoral associate of the Howard Hughes Medical Institute.
§
Associate investigator of the Howard Hughes Medical Institute. To
whom correspondence should be addressed: Howard Hughes Medical Inst.,
Section of Immunobiology, Yale University School of Medicine, 310 Cedar
St., Box 208011, New Haven, CT 06520-8011. Tel.: 203-737-2255; Fax:
203-737-1764; E-mail: david.schatz@yale.edu.
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