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

Carcinogenesis. 2006 Mar;27(3):446-53. doi: 10.1093/carcin/bgi254. Epub 2005 Oct 29.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antibiotics, Antineoplastic / pharmacology*
  • Cell Culture Techniques
  • Chromatin / metabolism
  • DNA Damage*
  • DNA Repair*
  • DNA-Binding Proteins / physiology
  • Endonucleases / physiology
  • Fibroblasts
  • Humans
  • Mitomycin / pharmacology*
  • Nuclear Proteins / physiology
  • Oxidative Stress
  • Transcription Factors / physiology


  • Antibiotics, Antineoplastic
  • Chromatin
  • DDB2 protein, human
  • DNA excision repair protein ERCC-5
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Transcription Factors
  • xeroderma pigmentosum group F protein
  • Mitomycin
  • Endonucleases