An in vivo analysis of MMC-induced DNA damage and its repair

Young Ju Lee, Su Jung Park, Samantha L.M. Ciccone, Chong Rak Kim, Suk Hee Lee

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Abstract

Mitomycin C (MMC) induces various types of DNA damages that cause significant cytotoxicity to cells. Accordingly, repair of MMC-induced damages involves multiple repair pathways such as nucleotide excision repair, homologous recombination repair and translesion bypass repair pathways. Nonetheless, repair of the MMC-induced DNA damages in mammals have not been fully delineated. In this study, we investigated potential roles for Xeroderma pigmentosum (XP) proteins in the repair of MMC-induced DNA damages using an assay that detects the ssDNA patches generated following treatment with MMC or 8′-methoxy-psoralen (8-MOP) + UVA (ultraviolet light A). Human wild-type cells formed distinctive ssDNA foci following treatment with MMC or 8-MOP + UVA, but not with those inducing alkylation damage, oxidative damage or strand-break damage, suggesting that the foci represent ssDNA patches formed during the crosslink repair. In contrast to wild-type cells, mutant defective in XPE orXPG did not form the ssDNA foci following MMC treatment, while XPF mutant cells showed a significantly delayed response in forming the foci. A positive role for XPG in the repair of MMC-induced DNA damages was further supported by observations that cells treated with MMC induced a tight association of XPG with chromatin, and a targeted inhibition of XPG abolished MMC-induced ssDNA foci formation, rendering cells hypersensitive to MMC. Together, our results suggest that XPG along with XPE and XPF play unique role(s) in the repair of MMC-induced DNA damages.

Original languageEnglish (US)
Pages (from-to)446-453
Number of pages8
JournalCarcinogenesis
Volume27
Issue number3
DOIs
StatePublished - Mar 1 2006

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ASJC Scopus subject areas

  • Cancer Research

Cite this

Lee, Y. J., Park, S. J., Ciccone, S. L. M., Kim, C. R., & Lee, S. H. (2006). An in vivo analysis of MMC-induced DNA damage and its repair. Carcinogenesis, 27(3), 446-453. https://doi.org/10.1093/carcin/bgi254