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.