Cloning the human and mouse MMS19 genes and functional complementation of a yeast mms19 deletion mutant

The MMS19 gene of the yeast Saccharomyces cerevisiae encodes a polypeptide of unknown function which is required for both nucleotide excision repair ( NER) and RNA polymerase II (RNAP II) transcription. Here we report the mole cular cloning of human and mouse orthologs of the yeast MMS19 gene. Both hu man and Drosophila MMS19 cDNAs correct thermosensitive growth and sensitivi ty to killing by UV radiation in a yeast mutant deleted for the MMS19 gene, indicating functional conservation between the yeast and mammalian gene pr oducts. Alignment of the translated sequences of MMS19 from multiple eukary otes, including mouse and human, revealed the presence of several conserved regions, including a HEAT repeat domain near the C-terminus, The presence of HEAT repeats, coupled with functional complementation of yeast mutant ph enotypes by the orthologous protein from higher eukaryotes, suggests a role of Mms19 protein in the assembly of a multiprotein complex(es) required fo r NER and RNAP II transcription. Both the mouse and human genes are ubiquit ously expressed as multiple transcripts, some of which appear to derive fro m alternative splicing. The ratio of different transcripts varies in severa l different tissue types.