Characterization of a DNA repair domain containing the dihydrofolate reductase gene in Chinese hamster ovary cells.

Bohr, Vilhelm A.; Okumoto, Diane S.; Ho, Linus; Hanawalt, Philip C.

doi:10.1016/s0021-9258(18)66617-7

Cited by 99 publications

(8 citation statements)

References 42 publications

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“…We expect adducts distributed all along the genomic DNA. This would not be favorable for repair, since a processive mode of action of repair enzymes is suggested (Bohr et al, 1986). Moreover, we observed that the exonuclease associated with the T4 DNA polymerase does not function easily on pyridopsoralen photoadducts.…”

Section: Mil2mentioning

confidence: 84%

“…This hypothesis has also been suggested for another damaging agent, (acetylamino)fluorene (Sage & Leng, 1980;Sage, 1981). In mammalian cells, some regions of the genome are preferentially repaired in comparison to others, probably in relation with the chromatin state (Bohr et al, 1986). The extent of psoralen adduct removal and repair synthesis in the nontranscribed a DNA is lower than in the bulk DNA [reviewed in Smith (1987)].…”

Section: Mil2mentioning

confidence: 99%

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Sequence specificity in photoreaction of various psoralen derivatives with DNA: role in biological activity

Boyer¹,

Moustacchi²,

Sage³

1988

Biochemistry

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The sequence specificity in the photoreaction of various psoralen derivatives with DNA is investigated by using DNA sequencing methodology. The 3'-5' exonuclease activity associated with T4 DNA polymerase serves as a probe to map the psoralens' photoaddition (monoadducts plus biadducts) on DNA fragments of defined sequence. This approach has already allowed us to demonstrate a strong sequence context effect on the 8-methoxypsoralen photobinding to DNA [Sage, E., & Moustacchi, E. (1987) Biochemistry 26, 3307-3314]. The psoralens studied include bifunctional derivatives [8-methoxypsoralen, 5-methoxypsoralen, and 4'-(hydroxymethyl)-4,5',8-trimethylpsoralen] and monofunctional derivatives (angelicin, 3-carbethoxypsoralen, and three pyridopsoralens). Maps of photochemical binding on two DNA fragments of the lacI gene of Escherichia coli are established for all the derivatives. These maps demonstrate the following general qualitative rules in the photoreaction of the furocoumarins with DNA: thymine residues in a GC environment are cold, adjacent thymines are better targets, 5'-TpA sites are strongly preferred versus 5'-ApT, and alternating (AT)n sequences are hot spots for photoaddition. Depending on the chemical structure of the derivatives and on their affinity for DNA, some minor differences in the binding spectrum are detected. A most interesting example is 3-carbethoxypsoralen, which specifically reacts with (AT)n sites. Our observations lead us to define two types of target sites: the "strong sites", which are preferential targets for all psoralen derivatives, and the "weak sites", which are targets only for derivatives having a high affinity for DNA. The frequency of DNA lesions is much higher in the former sites.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Mil2mentioning

confidence: 84%

Section: Mil2mentioning

confidence: 99%

Sequence specificity in photoreaction of various psoralen derivatives with DNA: role in biological activity

Boyer¹,

Moustacchi²,

Sage³

1988

Biochemistry

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“…Thus, although the intrinsic recognition and/or binding affinity of the cellular repair complex for these cross-links is poor, most of the cross-links are ultimately recognized and processed. This is in sharp contrast to the removal of UV-induced cyclobutane pyrimidine dimers in these cells; few if any of these lesions are removed from the extragenic fragment within 24 h (Bohr et al, 1986;Ho et al, 1989). Indeed, CHO Bn cells appear to be deficient in the repair of CPDs except in the transcribed strands of actively transcribed genes (Hanawalt, 1991).…”

Section: Discussionmentioning

confidence: 99%

Transcription-Coupled Repair of Psoralen Cross-Links but Not Monoadducts in Chinese Hamster Ovary Cells

Islas¹,

Baker²,

Hanawalt³

1994

Biochemistry

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We have examined the rate and extent of removal of 4'-(hydroxymethyl)-4,5',8-trimethylpsoralen (HMT) cross-linkable monoadducts and interstrand cross-links from restriction fragments within the amplicon containing the dihydrofolate reductase (DHFR) gene in the Chinese hamster ovary (CHO) cell line B11. The rate and extent of removal of HMT cross-links was significantly greater in an actively transcribed fragment than in a nontranscribed extragenic fragment of similar size. For the 5' half of the DHFR gene, approximately 80% of the HMT cross-links were removed in 8 h, in agreement with results reported by Vos and Wauthier [Vos, J. M., & Wauthier, E. L. (1991) Mol. Cell Biol. 11, 2245-2252, 1991]. However, few cross-links were removed in that period from the nontranscribed fragments, whose 5' end is approximately 7 kb downstream from the DHFR transcription unit and which includes a putative replication initiation site. Even after 24 h, only about 50% of the cross-links had been removed from this fragment. In contrast, both the rate and the extent of removal of cross-linkable HMT monoadducts were similar in the two fragments with 50% of the cross-linkable monoadducts removed in 24 h. Moreover, monoadducts formed in the bulk of the genome were removed in 24 h. Moreover, monoadducts formed in the bulk of the genome were removed at a slightly slower rate and to a lesser extent (30% in 24 hours) than those from either of these specific sequences.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…However, while repair of 8-oxoGua is more efficient in mitochondrial genes, compared to nuclear genes, in at least one study, no preference for transcribed genes over non-transcribed was noted, along with no strand preference [ 136 ]. Within genes, particular regions may be favoured, such as the 5′ portion of the DHFR gene [ 137 ], although the molecular basis for such differential repair across genes remains subject to speculation. This strand bias is now very well established, with transcription coupled-NER (TC-NER) being perhaps the most obvious example of a process leading to the biased removal of lesions [ 138 ], contributing to the heterogeneous distribution of damage and mutational, strand asymmetry in the cancer genome [ 139 ].…”

Section: Factors Influencing the Distribution Of Dna Damagementioning

confidence: 99%

Genome-wide mapping of genomic DNA damage: methods and implications

Amente

Scala

Majello

et al. 2021

Cell. Mol. Life Sci.

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Exposures from the external and internal environments lead to the modification of genomic DNA, which is implicated in the cause of numerous diseases, including cancer, cardiovascular, pulmonary and neurodegenerative diseases, together with ageing. However, the precise mechanism(s) linking the presence of damage, to impact upon cellular function and pathogenesis, is far from clear. Genomic location of specific forms of damage is likely to be highly informative in understanding this process, as the impact of downstream events (e.g. mutation, microsatellite instability, altered methylation and gene expression) on cellular function will be positional—events at key locations will have the greatest impact. However, until recently, methods for assessing DNA damage determined the totality of damage in the genomic location, with no positional information. The technique of “mapping DNA adductomics” describes the molecular approaches that map a variety of forms of DNA damage, to specific locations across the nuclear and mitochondrial genomes. We propose that integrated comparison of this information with other genome-wide data, such as mutational hotspots for specific genotoxins, tumour-specific mutation patterns and chromatin organisation and transcriptional activity in non-cancerous lesions (such as nevi), pre-cancerous conditions (such as polyps) and tumours, will improve our understanding of how environmental toxins lead to cancer. Adopting an analogous approach for non-cancer diseases, including the development of genome-wide assays for other cellular outcomes of DNA damage, will improve our understanding of the role of DNA damage in pathogenesis more generally.

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Characterization of a DNA repair domain containing the dihydrofolate reductase gene in Chinese hamster ovary cells.

Cited by 99 publications

References 42 publications

Sequence specificity in photoreaction of various psoralen derivatives with DNA: role in biological activity

Sequence specificity in photoreaction of various psoralen derivatives with DNA: role in biological activity

Transcription-Coupled Repair of Psoralen Cross-Links but Not Monoadducts in Chinese Hamster Ovary Cells

Genome-wide mapping of genomic DNA damage: methods and implications

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