Cloning of a human homolog of the yeast nucleotide excision repair gene MMS19 and interaction with transcription repair factor TFIIH via the XPB and XPD helicases
January 2000
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Nucleotide excision repair (NER) removes UV-induced photoproducts and numerous other DNA lesions in a highly conserved 'cut-and-paste' reaction that involves approximately 25 core components. In addition, several other proteins have been identified which are dispensable for NER in vitro but have an undefined role in vivo and may act at the interface of NER and other cellular processes. An intriguing example is the Saccharomyces cerevisiae Mms19 protein that has an unknown dual function in NER and RNA polymerase II transcription. Here we report the cloning and characterization of a human homolog, designated hMMS19, that encodes a 1030 amino acid protein with 26% identity and 51% similarity to S.cerevisiae Mms19p and with a strikingly similar size. The expression profile and nuclear location are consistent with a repair function. Co-immunoprecipitation experiments revealed that hMMS19 directly interacts with the XPB and XPD subunits of NER-transcription factor TFIIH. These findings extend the conservation of the NER apparatus and the link between NER and basal transcription and suggest that hMMS19 exerts its function in repair and transcription by interacting with the XPB and XPD helicases.
- Male
- Animals
- Cell Line
- Female
- Humans
- Research Support, Non-U.S. Gov't
- Protein Binding
- Amino Acid Sequence
- Cloning, Molecular
- DNA Repair/*genetics
- Molecular Sequence Data
- Sequence Alignment
- Hela Cells
- Phylogeny
- Gene Expression
- Sequence Homology, Amino Acid
- Blotting, Northern
- Chromosome Mapping
- DNA-Binding Proteins/metabolism
- In Situ Hybridization, Fluorescence
- Fungal Proteins/genetics
- Sequence Analysis, DNA
- *Transcription Factors, TFII
- Transcription Factors/*metabolism
- Tissue Distribution
- DNA Helicases/*metabolism
- RNA, Messenger/genetics/metabolism
- Transcription Factor TFIIH
- *Saccharomyces cerevisiae Proteins
- Xeroderma Pigmentosum Group D Protein
- Gene Expression Regulation, Developmental
- Chromosomes, Human, Pair 10/genetics
- DNA, Complementary/chemistry/genetics
- Proteins/*genetics/metabolism
- *TATA-Binding Protein Associated Factors
- *Transcription Factor TFIID
- hmms 19
- tfiih
- protein
- subunit
- antibody
- transcription
- yeast
- sf 9 cells
- sequence
- repair
- hoeijmaker
- acids research
- hmms 19 baculovirus
- mms 19
- helicase
- factor
- homolog
- function
- defect
- beads
