||V(D)J Recombinase-Mediated Deletion of the 'hprt' Gene in T-Lymphocytes from Adult Humans.
Fuscoe, J. C. ;
Zimmerman, L. J. ;
Harrington-Brock, K. ;
Burnette, L. ;
Moore, M. M. ;
||Health Effects Research Lab., Research Triangle Park, NC. ;Environmental Health Research and Testing, Inc., Research Triangle Park, NC. ;Vermont Univ., Burlington. Genetics Lab.
Hypoxanthine phosphoribosyltransferase ;
T-lymphocyte gene rearrangement ;
Chromosome deletion ;
Base sequence ;
DNA mutational analysis ;
Gene expression ;
Polymerase chain reaction ;
Southern blotting ;
Clone cells ;
||Most EPA libraries have a fiche copy filed under the call number shown. Check with individual libraries about paper copy.
The hprt T-cell cloning assay allows the detection of mutations occurring in vivo in the hypoxanthine guanine phosphoribosyltransferase (hprt) gene of T-lymphocytes. In the report, we examined a collection of 314 hprt-deficient clones derived from adult humans for evidence that the mutations were caused by the illegitimate activity of V(D)J recombinase by analyzing exons 2+3 deletion mutations. DNA sequence analysis of deletion breakpoint junctions showed that eight of the mutations were the result of V(D)J recombinase activity. The frequency of the recombinase-mediated mutations was similar in the adults and newborns (2-4 x 10 to the power of -7). Unregulated expression of V(D)J recombinase activity may be an important mechanism for genomic rearrangements in the genesis of cancer.