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Molecular and Cellular Biology, July 2000, p. 5032-5040, Vol. 20, No. 14
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Postcleavage Sequence Specificity in V(D)J Recombination

Emily A. Agard and Susanna M. Lewis*

Program in Genetics and Genomic Biology, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada M5G 1X8, and Department of Immunology, University of Toronto, Toronto, Ontario, Canada M5S 1A8

Received 16 March 2000/Returned for modification 7 April 2000/Accepted 24 April 2000

Unintended DNA rearrangements in a differentiating lymphocyte can have severe, oncogenic consequences, but the mechanisms for avoiding pathogenic outcomes in V(D)J recombination are not well understood. The first level at which fidelity is instituted is in discrimination by the recombination proteins between authentic and inauthentic recombination signal sequences. Nevertheless, this discrimination is not absolute and cannot fully eliminate targeting errors. To learn more about the basis of specificity during V(D)J recombination, we have investigated whether it is possible for the recombination machinery to detect an inaccurately targeted sequence subsequent to cleavage. These studies indicate that even postcleavage steps in V(D)J recombination are sequence specific and that noncanonical sequences will not efficiently support the resolution of recombination intermediates in vivo. Accordingly, interventions after a mistargeting event conceivably occur at a late stage in the joining process and the likelihood may well be crucial to enforcing fidelity during antigen receptor gene rearrangement.

* Corresponding author. Mailing address: Program in Genetics and Genomic Biology, Hospital for Sick Children Research Institute, 555 University Ave., Toronto, ON, Canada M5G 1X8. Phone: 416-813-8980. Fax: 416-813-8883. E-mail: susanna{at}sickkids.on.ca.

Molecular and Cellular Biology, July 2000, p. 5032-5040, Vol. 20, No. 14
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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