Effect of excision repair by diploid human fibroblasts on the kinds and locations of mutations induced by (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene in the coding region of the HPRT gene.

Chen, Ruey‐Hwa; Maher, Veronica M.; McCormick, J. Justin

doi:10.1073/pnas.87.21.8680

Cited by 116 publications

(48 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The coupling of transcription to repair helps to prevent such a catastrophe. Such coupling, although not universal for all adducts (22) or all genes (23), has been documented in vivo in several systems (4)(5)(6)(7)23), and it also has been inferred from studies showing selective mutagenesis (24,25 Partial purification of a coupling factor that enhances repair oftemplate DNA when added to a defined transcription-repair system. The defined system consisted ofpDR3274 irradiated with 225 Jm-2 of UV as the template-substrate for purified RNA Pol, UvrA, UvrB, UvrC, UvrD, pol I, and DNA ligase.…”

Section: Resultsmentioning

confidence: 99%

Gene- and strand-specific repair in vitro: partial purification of a transcription-repair coupling factor.

Selby

Sancar

1991

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

In eukaryotic and prokaryotic cells, actively transcribed genes and, in some instances, the template strand of these genes have been found to be repaired 2-10 times more rapidly than nontranscribed genes or the coding strand of transcribed genes. We demonstrate here gene-and template strand-specific repair synthesis in vitro by using an Eschenchia col cell-free extract and a plasmid carrying a gene with the strong tac promoter. Strand-specific repair of UV, 4'-hydroxymethyl-4,5',8-trimethylpsoralen, and cis-dicholorodiammine platinum(II) damage was dependent upon transcription and a functional nucleotide excision repair system and was stimulated by 6% (wt/vol) polyethylene glycol. A defined system consisting of the transcription and repair proteins in highly purified form did not perform strand-specific repair; however, active fractions of extract conferred strand specificity to the defied system. Transcription-repair coupling activity was partially purified from extract by successive DEAEagarose and gel filtration chromatography. The coupling factor is heat-labile, with an estimated Mr of 100,000.damaged DNA but does not take part in the DNA incision, which is carried out by UvrB-UvrC.] This study yielded a paradoxical result: RNA Pol stalled at a thymine dimer (TOT) in the template strand prevented access of (A)BC excinuclease (which incises the eighth phosphodiester bond 5' and the fifth phosphodiester bond 3' to the photodimer) to the lesion. Thus, a TOT in the complementary (coding) strand (which did not block transcription) was repaired 2-to 4-fold more efficiently than a TOT in the template strand (8). This result suggests that "transcription-repair coupling" (9) must accomplish two tasks: direct the repair enzyme (assembly) to the stalled complex and overcome the steric hindrance caused by the stalled RNA Pol. In this paper we show that a more complete but less-defined in vitro system utilizing E. coli cell-free extract carries out gene-and strand-specific repair. A coupling factor that conferred strand-specific repair function when added to a defined transcription-repair system was partially purified.DNA repair enzymes in general and nucleotide-excision nuclease subunits in particular are not abundant (1, 2), and it would be advantageous if the cell's limited resources were channeled to the most threatening genetic lesions. In this regard, while replication-blocking lesions could be lethal in any location on the chromosome, lesions in genes pose the additional threats of causing deleterious mutations or blocking transcription. It now appears that eukaryotes and prokaryotes use specific targeting mechanisms for some types of lesions to direct nucleotide-excision repair to regions most crucial for survival.The first and perhaps most influential report on the subject by Bohr et al. (3) showed that pyrimidine dimers (PyrOPyr) in the dihydrofolate reductase (DHFR) gene of Chinese Hamster ovary (CHO) cells were repaired about five times more rapidly than those in flanking nontranscribed regions or in...

show abstract

Section: Resultsmentioning

confidence: 99%

Gene- and strand-specific repair in vitro: partial purification of a transcription-repair coupling factor.

Selby

Sancar

1991

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…This concept was shown to be practical by Chen et ae. (15) using benzopyrene. Mimosine, a compound which inhibits molecules involved in generation of the START signal responsible for moving cells from G1 to S (16), provides a limited amount of protectiftn against the cytotoxicity of HD.…”

Section: Emmentioning

confidence: 99%

Cytometric Analysis of DNA Changes Induced by Sulfur Mustard

Smith

Sanders

Ruddle

et al. 1993

Journal of Toxicology: Cutaneous and Ocular Toxicology

View full text Add to dashboard Cite

“…B[a]PDE forms covalent DNA adducts primarily at the exocyclic N2 position of 2Ј-deoxyguanosine (dG). B[a]PDE-N2-dG adducts were found to induce the G to T transversion mutation (11)(12)(13), which is a molecular signature for cigarette smoke mutagens (2, 14 -16).…”

Section: Introductionmentioning

confidence: 99%

DNA Damage, Repair, and Mutation Induction by (+)- Syn and (−)- Anti -Dibenzo[ a,l ]Pyrene-11,12-Diol-13,14-Epoxides in Mouse Cells

et al. 2004

View full text Add to dashboard Cite

show abstract

Effect of excision repair by diploid human fibroblasts on the kinds and locations of mutations induced by (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene in the coding region of the HPRT gene.

Cited by 116 publications

References 30 publications

Gene- and strand-specific repair in vitro: partial purification of a transcription-repair coupling factor.

Gene- and strand-specific repair in vitro: partial purification of a transcription-repair coupling factor.

Cytometric Analysis of DNA Changes Induced by Sulfur Mustard

DNA Damage, Repair, and Mutation Induction by (+)- Syn and (−)- Anti -Dibenzo[ a,l ]Pyrene-11,12-Diol-13,14-Epoxides in Mouse Cells

Contact Info

Product

Resources

About