Involvement of mismatch repair in transcription-coupled nucleotide excision repair.
Nucleotide excision repair (NER) is a versatile repair pathway to remove a variety of DNA distorting lesions. NER operate via two subpathways, that are global genome repair (GGR) and transcription coupled nucleotide excision repair (TCR). GGR removes DNA damage from the genome over all, whilst TCR is selectively directed to DNA lesions in the transcribed strand of expressed genes. The damage recognition step in GGR and TCR is also different. In GGR, the XPC-HR23B complex is an essential factor to recruit proteins for subsequent process. In TCR, a stalled RNA polymerase II is a presumed trigger to initiate TCR machinery in concert with Cockayne syndrome (CS) proteins. Mismatch repair (MMR) keeps fidelity of DNA replication through correcting replication errors. A distinctive feature of MMR pathway is that this repair is directed exclusively to the newly synthesized strand. This characteristic contributes to mediation of cytotoxity by methylating agents, and MMR deficient cells are more resistant to methylating agents than MMR proficient cells. The interaction between MMR and NER has been reported by several investigators. However, the most controversial problem is the role of MMR in TCR TCR in E. coli requires the participation of the MutS and MutL MMR proteins. On the contrary, TCR in yeast is independent of the yeast MutS and MutL homologues. To date, in mammalian cells, there are conflicting evidences for the association of MMR with TCR pathway. The aim of this article is to provide a brief overview of the recent literature on this subject.
Kobayashi
Katsutoshi
K
Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan. casey@jikei.ac.jp
Karran
Peter
P
Oda
Shinya
S
Yanaga
Katsuhiko
K
D000818:Animals; D004249:DNA Damage; D053843:DNA Mismatch Repair; D004260:DNA Repair / Q000235:genetics / Q000502:physiology; D004261:DNA Replication; D006801:Humans; D012319:RNA Polymerase II; D014158:Transcription, Genetic
D012319:RNA Polymerase II