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The TFIIH subunit p89 (XPB) localizes to the centrosome during mitosis


Weber, A; Chung, H J; Springer, E; Heitzmann, D; Warth, R (2010). The TFIIH subunit p89 (XPB) localizes to the centrosome during mitosis. Cellular Oncology, 32(1-2):121-130.

Abstract

Background: The general transcription factor II H (TFIIH), comprised of a core complex and an associated CAK-complex, functions in transcription, DNA repair and cell cycle control. Mutations of the two largest subunits, p89 (XPB) and p80 (XPD), cause the hereditary cancer-prone syndrome xeroderma pigmentosum.Methods: The TFIIH subunit p89 was monitored during interphase and cell division by immunofluorescence staining, GFP-fusion constructs including deletions, live cell imaging and immuno-precipitations.Results: Here we demonstrate that during cell division, from prophase until telophase, the TFIIH core subunit p89, but not other subunits of TFIIH, associates with the centrosomes and the adjacent parts of the mitotic spindle. With overall constant levels throughout mitosis, p89 re-localizes to the newly formed nuclei by the end of mitosis. Furthermore, p89 interacts with the centrosomal protein gamma-tubulin. Truncations of p89 result in an abnormal subcellular distribution during interphase and abolished centrosomal association during mitosis.Conclusions: Our observations suggest a so far unappreciated role for p89 in cell cycle regulation, and may be the structural basis for a long known, but hitherto unexplained interaction between p89 and tubulin.

Abstract

Background: The general transcription factor II H (TFIIH), comprised of a core complex and an associated CAK-complex, functions in transcription, DNA repair and cell cycle control. Mutations of the two largest subunits, p89 (XPB) and p80 (XPD), cause the hereditary cancer-prone syndrome xeroderma pigmentosum.Methods: The TFIIH subunit p89 was monitored during interphase and cell division by immunofluorescence staining, GFP-fusion constructs including deletions, live cell imaging and immuno-precipitations.Results: Here we demonstrate that during cell division, from prophase until telophase, the TFIIH core subunit p89, but not other subunits of TFIIH, associates with the centrosomes and the adjacent parts of the mitotic spindle. With overall constant levels throughout mitosis, p89 re-localizes to the newly formed nuclei by the end of mitosis. Furthermore, p89 interacts with the centrosomal protein gamma-tubulin. Truncations of p89 result in an abnormal subcellular distribution during interphase and abolished centrosomal association during mitosis.Conclusions: Our observations suggest a so far unappreciated role for p89 in cell cycle regulation, and may be the structural basis for a long known, but hitherto unexplained interaction between p89 and tubulin.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Surgical Pathology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2010
Deposited On:26 Mar 2010 14:08
Last Modified:05 Apr 2016 14:03
Publisher:IOS Press
ISSN:1570-5870
Publisher DOI:https://doi.org/10.3233/CLO-2009-0509
PubMed ID:20208140

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