DNA-REPAIR DEFECTS ASSOCIATED WITH CHROMOSOMAL TRANSLOCATION BREAKSITE REGIONS

Using an assay that measures the removal of UV-induced pyrimidine dimers in specific DNA sequences, we have found that the Pvt-1, immunoglobulin H-C alpha (IgH-C alpha), and IgL-kappa loci are poorly repaired in normal B lymphoblasts from plasmacytoma-susceptible BALB-cAnPt mice. Breaksites in these genes are associated with the chromosomal translocations that are found in >95% of BALB-cAnPt plasmacytomas. In contrast to those from BALB/cAnPt mice, B lymphoblasts from plasmacytoma-resistant DBA-2N mice rapidly repair Pvt-1, IgH-C alpha, and IgL-kappa. Further, (BALB/cAnPt x DBA/2N)F-1 hybrids, which are resistant to plasmacytoma development, carry an efficient (DBA/2N-like) repair phenotype. Analysis of allele-specific repair in the IgH-C alpha locus indicates that efficient repair is controlled by dominant, trans-acting factors. In the F-1 heterozygotes, these factors promote efficient repair of BALB/cAnPt IgH-C alpha gen sequences. The same sequences are poorly repair in the BALB/cAnPt parental strain. Analysis of the strand specificity of repair indicates that both strand-selective and nonselective forms of repair determine repair efficiency at the gene level in nonimmortalized murine B lymphoblasts.