DNA Repair in the Metallothionein Gene Increases with Transcriptional Activation

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 1987 Dec 10

PMID 2827103

Citations 13

Authors

D S Okumoto

V A Bohr

Affiliations

Soon will be listed here.

Abstract

We have studied DNA repair in the Chinese Hamster Ovary (CHO) metallothionein (MT) gene after UV-light induced damage. The repair was examined comparatively with or without transcriptional activation of the gene by incubation in the presence of the heavy metal ZnCl2. Whereas the repair efficiency was very low in the uninduced state, it increased significantly after induction of the gene. The presence of ZnCl2 did not appear to change other repair parameters in the cells. The overall genome DNA repair efficiency after UV irradiation was similar whether or not the gene was induced and the preferential DNA repair pattern in the essential dihydrofolate reductase (DHFR) gene which we have previously described was unaffected by the presence of ZnCl2. Based upon repair analysis in two different restriction fragments containing the MT I gene, we conclude that the region of efficient repair after induction is considerably larger than the 1 kb size of the gene. The results suggest that the accessibility of a genomic region to DNA repair enzymes may be regulated by the local chromatin structure in a dynamic manner.

Citing Articles

Homogenous repair of singlet oxygen-induced DNA damage in differentially transcribed regions and strands of human mitochondrial DNA.

Anson R, Croteau D, Stierum R, Filburn C, PARSELL R, Bohr V Nucleic Acids Res. 1998; 26(2):662-8.

PMID: 9421531 PMC: 147305. DOI: 10.1093/nar/26.2.662.

DNA repair defects associated with chromosomal translocation breaksite regions.

Beecham E, Jones G, Link C, Huppi K, Potter M, MUSHINSKI J Mol Cell Biol. 1994; 14(2):1204-12.

PMID: 8289801 PMC: 358476. DOI: 10.1128/mcb.14.2.1204-1212.1994.

Preferential repair of UV damage in highly transcribed DNA diminishes UV-induced intrachromosomal recombination in mammalian cells.

Deng W, Nickoloff J Mol Cell Biol. 1994; 14(1):391-9.

PMID: 8264606 PMC: 358388. DOI: 10.1128/mcb.14.1.391-399.1994.

Differential repair of DNA damage in the human metallothionein gene family.

Leadon S, Snowden M Mol Cell Biol. 1988; 8(12):5331-8.

PMID: 3149714 PMC: 365635. DOI: 10.1128/mcb.8.12.5331-5338.1988.

Compositional patterns in vertebrate genomes: conservation and change in evolution.

Mouchiroud D, Gautier C, Bernardi G J Mol Evol. 1988; 28(1-2):7-18.

PMID: 3148744 DOI: 10.1007/BF02143493.

References

Ali R, SAUERBIER W . Effects of ultraviolet irradiation and postirradiation incubation on heterogenous nuclear RNA size in murine cells. Biophys J. 1978; 22(3):393-411. PMC: 1473483. DOI: 10.1016/s0006-3495(78)85495-2. View

Griffith B, WALTERS R, Enger M, Hildebrand C, Griffith J . cDNA cloning and nucleotide sequence comparison of Chinese hamster metallothionein I and II mRNAs. Nucleic Acids Res. 1983; 11(3):901-10. PMC: 325761. DOI: 10.1093/nar/11.3.901. View

Reeves R . Transcriptionally active chromatin. Biochim Biophys Acta. 1984; 782(4):343-93. DOI: 10.1016/0167-4781(84)90044-7. View

Mullenders L, van Kesteren A, Bussmann C, van Zeeland A, Natarajan A . Preferential repair of nuclear matrix associated DNA in xeroderma pigmentosum complementation group C. Mutat Res. 1984; 141(2):75-82. DOI: 10.1016/0165-7992(84)90014-9. View

Bohr V, Smith C, Okumoto D, HANAWALT P . 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. Cell. 1985; 40(2):359-69. DOI: 10.1016/0092-8674(85)90150-3. View

Crawford B, Enger M, Griffith B, Griffith J, Hanners J, Longmire J . Coordinate amplification of metallothionein I and II genes in cadmium-resistant Chinese hamster cells: implications for mechanisms regulating metallothionein gene expression. Mol Cell Biol. 1985; 5(2):320-9. PMC: 366715. DOI: 10.1128/mcb.5.2.320-329.1985. View

Madhani H, Bohr V, HANAWALT P . Differential DNA repair in transcriptionally active and inactive proto-oncogenes: c-abl and c-mos. Cell. 1986; 45(3):417-23. DOI: 10.1016/0092-8674(86)90327-2. View

Bohr V, Okumoto D, HANAWALT P . Survival of UV-irradiated mammalian cells correlates with efficient DNA repair in an essential gene. Proc Natl Acad Sci U S A. 1986; 83(11):3830-3. PMC: 323617. DOI: 10.1073/pnas.83.11.3830. View

Hamer D . Metallothionein. Annu Rev Biochem. 1986; 55:913-51. DOI: 10.1146/annurev.bi.55.070186.004405. View

10.

Griffith J . Coordinate expression of amplified metallothionein I and II genes in cadmium-resistant Chinese hamster cells. Mol Cell Biol. 1985; 5(12):3525-31. PMC: 369183. DOI: 10.1128/mcb.5.12.3525-3531.1985. View

11.

Bohr V, Okumoto D, Ho L, HANAWALT P . Characterization of a DNA repair domain containing the dihydrofolate reductase gene in Chinese hamster ovary cells. J Biol Chem. 1986; 261(35):16666-72. View

12.

Mellon I, Bohr V, Smith C, HANAWALT P . Preferential DNA repair of an active gene in human cells. Proc Natl Acad Sci U S A. 1986; 83(23):8878-82. PMC: 387036. DOI: 10.1073/pnas.83.23.8878. View