Selective removal of transcription-blocking DNA damage from the transcribed strand of the mammalian DHFR gene

@article{Mellon1987SelectiveRO,
  title={Selective removal of transcription-blocking DNA damage from the transcribed strand of the mammalian DHFR gene},
  author={Isabel Mellon and Graciela Spivak and Philip C. Hanawalt},
  journal={Cell},
  year={1987},
  volume={51},
  pages={241-249}
}
We find a dramatic difference in the efficiency of removal of UV-induced pyrimidine dimers from the transcribed and nontranscribed strands of the dihydrofolate reductase (DHFR) gene in cultured hamster and human cells. In hamster cells, 80% of the dimers are removed from the transcribed strand in 4 hr, but little repair occurs in the nontranscribed strand even after 24 hr. In human cells, repair is significantly faster in the transcribed strand than in the other strand. Furthermore, in the 5… Expand
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Transcription-coupled and Transcription-independent Repair of Cyclobutane Pyrimidine Dimers in the Dihydrofolate Reductase Gene*
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References

SHOWING 1-10 OF 38 REFERENCES
Preferential DNA repair of an active gene in human cells.
TLDR
The finding of preferential early repair in a transcriptionally active region in overall repair-proficient cells suggests that selective dimer removal from active sequences may be a general characteristic of mammalian DNA repair. Expand
DNA repair in an active gene: Removal of pyrimidine dimers from the DHFR gene of CHO cells is much more efficient than in the genome overall
TLDR
DNA repair was measured in the dihydrofolate reductase gene in Chinese hamster ovary cells by quantitating pyrimidine dimers with a specific UV-endonuclease, suggesting preferential repair of vital sequences facilitates UV-resistance of these cells despite low overall repair levels. Expand
Characterization of a DNA repair domain containing the dihydrofolate reductase gene in Chinese hamster ovary cells.
TLDR
It is found that the only hypomethylated sites in and around the DHFR gene were in the fragment near its 5' end, which displayed maximal DNA repair efficiency, and the size of the region of preferential DNA repair at the DH FR locus appears to be in the range of 50-80 kilobases. Expand
Differential DNA repair in transcriptionally active and inactive proto-oncogenes: c-abl and c-mos
TLDR
This is the first demonstration of differential DNA repair in two different genes, and these findings have important implications for the mechanisms of proto-oncogene activation. Expand
UV Damage at the Transcriptional Level
TLDR
It has been shown that upon irradiation of the template DNA, shorter RNA chains are produced and transcription of promotor-distal parts of scriptons decreases preferentially, and similar conclusions are reached in studies with in vivo transcriptions of UV-irradiated bacteriophage and bacterial DNA and in vivo transcripts in eukaryotic cells. Expand
Survival of UV-irradiated mammalian cells correlates with efficient DNA repair in an essential gene.
TLDR
A newly developed technique to measure dimer frequencies in single-copy specific sequences suggests a correlation between efficient repair of essential genes and resistance to DNA-damaging agents such as UV light. Expand
The functional human dihydrofolate reductase gene.
Molecular cloning, mapping, and DNA sequencing techniques have been used to characterize the functional human dihydrofolate reductase (DHFR) gene. The gene is about 30 kilobases in length. Its codingExpand
Multiple transcription start sites, DNase I-hypersensitive sites, and an opposite-strand exon in the 5' region of the CHO dhfr gene.
TLDR
Each of the three mammalian dhfr genes has several G-rich GC boxes proximal to the major dhfr transcription start site and several GC boxes of the opposite orientation (C rich) in a distal region about 500 bp upstream. Expand
A novel repair enzyme: UVRABC excision nuclease of Escherichia coli cuts a DNA strand on both sides of the damaged region
TLDR
Evidence is obtained suggesting that the UVRABC nuclease acts by the same mechanism on PydC photoproducts which are thought to be of primary importance in UV-induced mutagenesis. Expand
Analysis of the mouse dhfr promoter region: existence of a divergently transcribed gene.
The use of murine dihydrofolate reductase (dhfr) gene amplification mutants enabled us to identify important structural and functional features of the dhfr promoter region. We found anotherExpand
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