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Human mediator MED 17 subunit plays essential roles in gene regulation by associating with the transcription and DNA repair machineries
Author(s) -
Kikuchi Yuko,
Umemura Hiroyasu,
Nishitani Saori,
Iida Satoshi,
Fukasawa Rikiya,
Hayashi Hiroto,
Hirose Yutaka,
Tanaka Aki,
Sugasawa Kaoru,
Ohkuma Yoshiaki
Publication year - 2015
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12210
Subject(s) - transcription factor ii h , biology , nucleotide excision repair , rna polymerase ii , helicase , transcription (linguistics) , microbiology and biotechnology , protein subunit , dna repair , gene , genetics , promoter , rna , gene expression , linguistics , philosophy
In eukaryotes, holo‐Mediator consists of four modules: head, middle, tail, and CDK /Cyclin. The head module performs an essential function involved in regulation of RNA polymerase II (Pol II). We studied the human head module subunit MED 17 ( hMED 17). Recent structural studies showed that yeast MED 17 may function as a hinge connecting the neck and movable jaw regions of the head module to the fixed jaw region. Luciferase assays in hMED 17‐knockdown cells showed that hMED 17 supports transcriptional activation, and pulldown assays showed that hMED 17 interacted with Pol II and the general transcription factors TFIIB , TBP , TFIIE , and TFIIH . In addition, hMED 17 bound to a DNA helicase subunit of TFIIH , XPB , which is essential for both transcription and nucleotide excision repair ( NER ). Because hMED 17 associates with p53 upon UV ‐C irradiation, we treated human MCF ‐7 cells with either UV ‐C or the MDM 2 inhibitor Nutlin‐3. Both treatments resulted in accumulation of p53 in the nucleus, but hMED 17 remained concentrated in the nucleus in response to UV ‐C. hMED 17 colocalized with the NER factors XPB and XPG following UV ‐C irradiation, and XPG and XPB bound to hMED 17 in vitro . These findings suggest that hMED 17 may play essential roles in switching between transcription and NER .