MMS19 Nucleotide Excision Repair Homolog (MMS19)

MMS19 is required for NER and Pol II transcription, but its precise role in each process is unknown. The human MMS19 gene originates multiple splice variants, some of which may encode distinct MMS19 protein isoforms. MMS19 splice variants are conserved across species and are functionally distinct. Expression of human MMS19 splice variants in mms19-deleted yeast cells produced unique patterns of thermosensitivity and ultraviolet radiation-sensitivity that point to three MMS19 structural domains with distinct in vivo functions. MMS19 polypeptides lacking domain A are able to fulfill the role of full-length MMS19 in NER but not in transcription. MMS19 polypeptides lacking part of domain B are efficient in transcription but not in NER. MMS19 polypeptides lacking domain C (HEAT repeats) are unable to fulfill either function.