Postcleavage sequence specificity in V(D)J recombination.

Abstract:

: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.

journal_name

Mol Cell Biol

authors

Agard EA,Lewis SM

doi

10.1128/mcb.20.14.5032-5040.2000

subject

Has Abstract

pub_date

2000-07-01 00:00:00

pages

5032-40

issue

14

eissn

0270-7306

issn

1098-5549

journal_volume

20

pub_type

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