Carcinogenesis, Vol 18, 687-694, Copyright © 1997 by Oxford University Press
EJ Beecham, JD Owens, JD Shaughnessy Jr, K Huppi, VA Bohr and JF Mushinski
Preferential repair of pyrimidine dimers in rodent cells is thought to be
directly coupled to the RNA transcription machinery. The most compelling
evidence for this notion is the finding that excision repair occurs more
rapidly in the template strand of DNA of transcribed genes than in the
non-template strand. A thorough test of this coupling concept by careful
comparison of the rate of repair to the rate of transcription of a gene and
its regulatory region has not been reported. In the present study, we used
nuclear run-on as a measure of transcription in the c-myc and Pvt1 genes in
normal B-lymphoblasts from plasmacytoma-susceptible (BALB/cAnPt) and
plasmacytoma-resistant (DBA/2N) strains of mice. Previous studies have
shown that these loci, but not c-abl or Dhfr are repaired differently in
mouse strains: poorly in BALB/cAnPt but efficiently in DBA/2N. The results
presented here indicate that in DBA/2N cells, run-on transcription from
both DNA strands can be readily detected in the regions of c-myc and Pvt1
that were efficiently repaired. Unexpectedly, however, in BALB/cAnPt
lymphoblasts, transcription was equivalent to that of DBA/2N, despite a
dramatic reduction in efficiency of excision repair. This finding indicates
that, in BALB/cAnPt lymphoblasts, DNA repair 5' to c-myc and in Pvt1 is
decoupled from the RNA transcription machinery. We postulate that this
dissociation of repair and transcription represents a BALB/cAnPt-specific
defect in a component of the transcription/repair complex that specifically
compromises repair activity but not transcription. This defect may be
responsible for the inability of normal BALB/cAnPt lymphoblasts to repair
DNA sequences in the c-myc 5' flank and the Pvt1 gene, inducing
gene-specific instability that predisposes these loci to genetic accidents,
including chromosomal translocation, retroviral integration and other
mutations.
ARTICLES
Decoupling of DNA excision repair and RNA transcription in translocation breaksite regions of plasmacytoma-susceptible BALB/cAnPt mice
Laboratory of Molecular Pharmacology, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Felix, A. Polack, W. Pretsch, S. H. Jackson, L. Feigenbaum, G.-W. Bornkamm, and S. Janz Moderate Hypermutability of a Transgenic lacZ Reporter Gene in Myc-Dependent Inflammation-Induced Plasma Cell Tumors in Mice Cancer Res., January 15, 2004; 64(2): 530 - 537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Felix, K. A. Kelliher, G.-W. Bornkamm, and S. Janz Elevated Mutant Frequencies in Lymphoid Tissues Persist throughout Plasmacytoma Development in BALB/c.{{lambda}}LIZ Mice Cancer Res., August 1, 1999; 59(15): 3621 - 3626. [Abstract] [Full Text] [PDF]
|
|