Repair of O6-methylguanine in DNA by Demethylation is Lacking in Mer- Human Tumor Cell Strains

Overview

Journal Carcinogenesis

Specialty Oncology

Date 1983 Jan 1

PMID 6825208

Citations 26

Authors

D B Yarosh

R S Foote

S Mitra

R S Day 3rd

Affiliations

Soon will be listed here.

Abstract

The ability of extracts of human tumor cells to demethylate O6-methylguanine (O6-MeG) in DNA was assayed using the synthetic DNA polymer poly(dC,dG,m6dG). Cell strains proficient in repair of O6-MeG in vivo (Mer+ phenotype) contained a methyltransferase activity while repair deficient cells (Mer- phenotype) had little or no activity. Mixing extracts of different Mer- strains did not result in the appearance of the activity. Extracts of Mer- cells did not inhibit the activity in extracts of Mer+ cells. Both Mer+ and Mer- strains contained methylnitrosourea-damage-specific endonuclease activity. The data suggest that the Mer- strains are deficient in methyltransferase and that this is the fundamental reason for their hypersensitivity to the cytotoxic effects of DNA alkylation. The activity was partially purified from a Mer+ colon carcinoma cell strain. Its kinetics parallel the repair of O6-MeG in DNA in vivo and suggest that the activity is inactivated during repair of DNA.

Citing Articles

Variant allelic frequencies of driver mutations can identify gliomas with potentially false-negative MGMT promoter methylation results.

McCord M, Jamshidi P, Thirunavu V, Santana-Santos L, Vormittag-Nocito E, Dittman D Acta Neuropathol Commun. 2023; 11(1):175.

PMID: 37919784 PMC: 10623846. DOI: 10.1186/s40478-023-01680-0.

Crosstalk between repair pathways elicits double-strand breaks in alkylated DNA and implications for the action of temozolomide.

Fuchs R, Isogawa A, Paulo J, Onizuka K, Takahashi T, Amunugama R Elife. 2021; 10.

PMID: 34236314 PMC: 8289412. DOI: 10.7554/eLife.69544.

Genotoxic anti-cancer agents and their relationship to DNA damage, mitosis, and checkpoint adaptation in proliferating cancer cells.

Swift L, Golsteyn R Int J Mol Sci. 2014; 15(3):3403-31.

PMID: 24573252 PMC: 3975345. DOI: 10.3390/ijms15033403.

Peritoneal carcinomatosis from ovarian cancer: chemosensitivity test and tissue markers as predictors of response to chemotherapy.

Arienti C, Tesei A, Verdecchia G, Framarini M, Virzi S, Grassi A J Transl Med. 2011; 9:94.

PMID: 21689426 PMC: 3141502. DOI: 10.1186/1479-5876-9-94.

p53-Mediated down-regulation of the human DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT) via interaction with Sp1 transcription factor.

Bocangel D, Sengupta S, Mitra S, Bhakat K Anticancer Res. 2009; 29(10):3741-50.

PMID: 19846904 PMC: 2814523.