DNA repair in the c-myc proto-oncogene locus: possible involvement in susceptibility or resistance to plasmacytoma induction in BALB/c mice.
This report describes an unexpected difference in the efficiency of removal of UV-induced DNA damage in the c-myc locus in splenic B lymphoblasts from two inbred strains of mice. In cells from plasmacytoma-resistant DBA/2N mice, 35% of UV-induced damage in the regulatory and 5' flank of c-myc is removed by 12 h. However, in cells from plasmacytoma-susceptible BALB/cAn mice, damage is not removed from this region. In the protein-encoding region and 3' flank of c-myc as well as in two dihydrofolate reductase gene fragments, UV damage is repaired with similar efficiency in B lymphoblasts from both strains of mice. Furthermore, in the protein-encoding portion and 3' flank of c-myc, damage is selectively removed from only the transcribed strand. No repair is detected in the nontranscribed strand. In contrast, DNA repair in the 5' flank of c-myc is not strand specific; in DNA from DBA/2N cells, UV damage is rapidly removed from both the transcribed and nontranscribed strands. In BALB/cAn cells no repair was detected in either strand in the 5'flank, consistent with the results with double-stranded, nick-translated probes to this region of c-myc. In addition to the repair studies, we have detected post-UV-damage formation: in most of the genes studied, we find that additional T4 endonuclease-sensitive sites are formed in the DNA 2 h after irradiation. Our findings provide new insights into the details of gene-specific and strand-specific DNA repair and suggest that there may be close links between DNA repair and B-cell neoplastic development.
Beecham
E J
EJ
Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, Maryland 20892.
Mushinski
J F
JF
Shacter
E
E
Potter
M
M
Bohr
V A
VA
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology / Q000528:radiation effects; D015152:Blotting, Northern; D004247:DNA / Q000235:genetics / Q000302:isolation & purification / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair / Q000528:radiation effects; D004261:DNA Replication; D016259:Genes, myc; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D010954:Plasmacytoma / Q000235:genetics* / Q000276:immunology; D011519:Proto-Oncogenes; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D015183:Restriction Mapping; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D014466:Ultraviolet Rays
D012313:RNA; D004247:DNA; D013762:Tetrahydrofolate Dehydrogenase