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.
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.
Seroz
T
T
MGC-Department of Cell Biology and Genetics, Center for Biomedical Genetics, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
Winkler
G S
GS
Auriol
J
J
Verhage
R A
RA
Vermeulen
W
W
Smit
B
B
Brouwer
J
J
Eker
A P
AP
Weeda
G
G
Egly
J M
JM
Hoeijmakers
J H
JH
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D003001:Cloning, Molecular; D004265:DNA Helicases / Q000378:metabolism*; D004260:DNA Repair / Q000235:genetics*; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005656:Fungal Proteins / Q000235:genetics; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D006367:HeLa Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D035381:TATA-Binding Protein Associated Factors; D014018:Tissue Distribution; D035362:Transcription Factor TFIID; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000378:metabolism*; D019473:Transcription Factors, TFII; D051759:Xeroderma Pigmentosum Group D Protein
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C103317:MET18 protein, S cerevisiae; C416322:MMS19 protein, human; D011506:Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C490039:TAF6 protein, S cerevisiae; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; D014157:Transcription Factors; D019473:Transcription Factors, TFII; C072022:XPBC-ERCC-3 protein; D051758:Transcription Factor TFIIH; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human