Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.5.1.3 (
dihydrofolate reductase
)
5,819
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
It has been long recognized that in mammalian cells, DNA damage is preferentially repaired in the transcribed strand of transcriptionally active genes. However, recently, we found that in Chinese hamster ovary (CHO) cells, UV-induced cyclobutane pyrimidine dimers (CPDs) are preferentially repaired in both the transcribed and the non-transcribed strand of exon 1 of the
dihydrofolate reductase
(
DHFR
) gene. We mapped CPD repair at the nucleotide level in the transcriptionally active
DHFR
gene and the adjacent upstream
OST
gene, both of which have been translocated to two chromosomal positions that differ from their normal endogeneous positions. This allowed us to study the role of transcription, genomic context and chromatin structure on repair. We found that CPD repair in the transcribed strand is the same for endogenous and translocated
DHFR
genes, and the order of repair efficiency is exon 1 > exon 2 > exon 5. However, unlike the endogenous
DHFR
gene, efficient repair of CPDs in the non-transcribed strand of exon 1 is not observed in the translocated
DHFR
gene. CPDs are efficiently repaired in the transcribed strand in endogenous and translocated
OST
genes, which indicates that efficient repair in exon 1 of the non-transcribed strand of the endogenous
DHFR
gene is not due to the extension of transcription-coupled repair of the
OST
gene. Using micrococcal nuclease digestion, we probed the chromatin structure in the
DHFR
gene and found that chromatin structure in the exon 1 region of endogenous
DHFR
is much more open than at translocated loci. These results suggest that while transcription-coupled repair is transcription dependent, global genomic repair is greatly affected by chromatin structure.
...
PMID:Effects of genomic context and chromatin structure on transcription-coupled and global genomic repair in mammalian cells. 1453 Apr 38
