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)F1 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 F1 heterozygotes, these factors promote efficient repair of BALB/cAnPt IgH-C alpha gene sequences. The same sequences are poorly repaired 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.
Beecham
E J
EJ
Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, Maryland 20892.
Jones
G M
GM
Link
C
C
Huppi
K
K
Potter
M
M
Mushinski
J F
JF
Bohr
V A
VA
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured; D003433:Crosses, Genetic; D004247:DNA / Q000235:genetics / Q000302:isolation & purification / Q000528:radiation effects*; D004260:DNA Repair / Q000235:genetics*; D004261:DNA Replication; D005803:Genes, Immunoglobulin; D016313:Genes, abl; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate / Q000235:genetics; D007134:Immunoglobulin Switch Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D010954:Plasmacytoma / Q000235:genetics / Q000276:immunology; D011740:Pyrimidine Dimers; D015183:Restriction Mapping; D014178:Translocation, Genetic; D014466:Ultraviolet Rays
D007145:Immunoglobulin kappa-Chains; D011740:Pyrimidine Dimers; D004247:DNA