Mismatch repair participates in error-free processing of DNA interstrand crosslinks in human cells.
DNA interstrand crosslinks (ICLs) present formidable blocks to DNA metabolic processes and must be repaired for cell survival. ICLs are induced in DNA by intercalating compounds such as the widely used therapeutic agent psoralen. In bacteria, both nucleotide excision repair (NER) and homologous recombination are required for the repair of ICLs. The processing of ICLs in mammalian cells is not clearly understood. However, it is known that processing can occur by NER, which for psoralen ICLs can be an error-generating process conducive to mutagenesis. We show here that another repair pathway, mismatch repair (MMR), is also involved in eliminating psoralen ICLs in human cells. MMR deficiency renders cells hypersensitive to psoralen ICLs without diminishing their mutagenic potential, suggesting that MMR does not contribute to error-generating repair, and that MMR may represent a relatively error-free mechanism for processing these lesions in human cells. Thus, enhancement of MMR relative to NER may reduce the mutagenesis caused by DNA ICLs in humans.
Wu
Qi
Q
Department of Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, 1808 Park Road 1-C, Smithville, Texas 78957, USA.
Christensen
Laura A
LA
Legerski
Randy J
RJ
Vasquez
Karen M
KM
D020137:Base Pair Mismatch / Q000235:genetics*; D001483:Base Sequence; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents / Q000633:toxicity; D004247:DNA / Q000737:chemistry*; D004252:DNA Mutational Analysis; D004260:DNA Repair; D004926:Escherichia coli; D005363:Ficusin / Q000633:toxicity; D016153:Genes, Suppressor; D006801:Humans; D008969:Molecular Sequence Data; D009841:Oligonucleotides; D010957:Plasmids / Q000235:genetics; D012343:RNA, Transfer / Q000235:genetics; D017422:Sequence Analysis, DNA; D014162:Transfection; D014466:Ultraviolet Rays
D003432:Cross-Linking Reagents; D009841:Oligonucleotides; C096275:supF tRNA; D004247:DNA; D012343:RNA, Transfer; D005363:Ficusin