XPC lymphoblastoid cells defective in hMutS¿ DNA mismatch repair complex exhibit normal sensitivity to UVC radiation and normal transcription-coupled excision repair of DNA cyclobutane pyrimidine dimers.

Nucleotide excision (NER) is generally considered to comprise two partially distinct subpathways. Global genomic repair (GGR) removes damage from the genome overall and transcription-coupled repair (TCR) selectively excises damage from transcribed DNA. Cells from individuals belonging to xeroderma pigmentosum (XP) complementation group C are defective in GGR but retain a functional TCR pathway. DNA mismatch repair (MMR) corrects replication errors but can also process DNA damage. It has been suggested that the essential hMutSa and hMutLa MMR protein complexes are also required for effective excision of UV-induced cyclobutane pyrimidine dimers (CPD) by TCR. We have combined an MMR and an XPC defect in a human lymphoblastoid cell line. The MMR-defective XPC cells were defective in the hMutSa mismatch recognition complex that comprises hMSH2 and hMSH6. They were not detectably more sensitive to killing by UV than their MMR proficient counterparts and were able to excise CPDs from an actively transcribed DNA strand. We conclude efficient TCR does not depend on a functional hMutSa complex.