Dynamic interaction of TTDA with TFIIH is stabilized by nucleotide excision repair in living cells.

Transcription/repair factor IIH (TFIIH) is essential for RNA polymerase II transcription and nucleotide excision repair (NER). This multi-subunit complex consists of ten polypeptides, including the recently identified small 8-kDa trichothiodystrophy group A (TTDA)/ hTFB5 protein. Patients belonging...

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Autores principales:	Giuseppina Giglia-Mari, Catherine Miquel, Arjan F Theil, Pierre-Olivier Mari, Deborah Hoogstraten, Jessica M Y Ng, Christoffel Dinant, Jan H J Hoeijmakers, Wim Vermeulen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2006
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/9b5cec00a6f2471d8895e60b61883ddf
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spelling	oai:doaj.org-article:9b5cec00a6f2471d8895e60b61883ddf2021-11-25T05:33:09ZDynamic interaction of TTDA with TFIIH is stabilized by nucleotide excision repair in living cells.1544-91731545-788510.1371/journal.pbio.0040156https://doaj.org/article/9b5cec00a6f2471d8895e60b61883ddf2006-06-01T00:00:00Zhttps://doi.org/10.1371/journal.pbio.0040156https://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Transcription/repair factor IIH (TFIIH) is essential for RNA polymerase II transcription and nucleotide excision repair (NER). This multi-subunit complex consists of ten polypeptides, including the recently identified small 8-kDa trichothiodystrophy group A (TTDA)/ hTFB5 protein. Patients belonging to the rare neurodevelopmental repair syndrome TTD-A carry inactivating mutations in the TTDA/hTFB5 gene. One of these mutations completely inactivates the protein, whereas other TFIIH genes only tolerate point mutations that do not compromise the essential role in transcription. Nevertheless, the severe NER-deficiency in TTD-A suggests that the TTDA protein is critical for repair. Using a fluorescently tagged and biologically active version of TTDA, we have investigated the involvement of TTDA in repair and transcription in living cells. Under non-challenging conditions, TTDA is present in two distinct kinetic pools: one bound to TFIIH, and a free fraction that shuttles between the cytoplasm and nucleus. After induction of NER-specific DNA lesions, the equilibrium between these two pools dramatically shifts towards a more stable association of TTDA to TFIIH. Modulating transcriptional activity in cells did not induce a similar shift in this equilibrium. Surprisingly, DNA conformations that only provoke an abortive-type of NER reaction do not result into a more stable incorporation of TTDA into TFIIH. These findings identify TTDA as the first TFIIH subunit with a primarily NER-dedicated role in vivo and indicate that its interaction with TFIIH reflects productive NER.Giuseppina Giglia-MariGiuseppina Giglia-MariCatherine MiquelArjan F TheilPierre-Olivier MariDeborah HoogstratenJessica M Y NgChristoffel DinantJan H J HoeijmakersWim VermeulenPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 4, Iss 6, p e156 (2006)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Giuseppina Giglia-Mari Giuseppina Giglia-Mari Catherine Miquel Arjan F Theil Pierre-Olivier Mari Deborah Hoogstraten Jessica M Y Ng Christoffel Dinant Jan H J Hoeijmakers Wim Vermeulen Dynamic interaction of TTDA with TFIIH is stabilized by nucleotide excision repair in living cells.
description	Transcription/repair factor IIH (TFIIH) is essential for RNA polymerase II transcription and nucleotide excision repair (NER). This multi-subunit complex consists of ten polypeptides, including the recently identified small 8-kDa trichothiodystrophy group A (TTDA)/ hTFB5 protein. Patients belonging to the rare neurodevelopmental repair syndrome TTD-A carry inactivating mutations in the TTDA/hTFB5 gene. One of these mutations completely inactivates the protein, whereas other TFIIH genes only tolerate point mutations that do not compromise the essential role in transcription. Nevertheless, the severe NER-deficiency in TTD-A suggests that the TTDA protein is critical for repair. Using a fluorescently tagged and biologically active version of TTDA, we have investigated the involvement of TTDA in repair and transcription in living cells. Under non-challenging conditions, TTDA is present in two distinct kinetic pools: one bound to TFIIH, and a free fraction that shuttles between the cytoplasm and nucleus. After induction of NER-specific DNA lesions, the equilibrium between these two pools dramatically shifts towards a more stable association of TTDA to TFIIH. Modulating transcriptional activity in cells did not induce a similar shift in this equilibrium. Surprisingly, DNA conformations that only provoke an abortive-type of NER reaction do not result into a more stable incorporation of TTDA into TFIIH. These findings identify TTDA as the first TFIIH subunit with a primarily NER-dedicated role in vivo and indicate that its interaction with TFIIH reflects productive NER.
format	article
author	Giuseppina Giglia-Mari Giuseppina Giglia-Mari Catherine Miquel Arjan F Theil Pierre-Olivier Mari Deborah Hoogstraten Jessica M Y Ng Christoffel Dinant Jan H J Hoeijmakers Wim Vermeulen
author_facet	Giuseppina Giglia-Mari Giuseppina Giglia-Mari Catherine Miquel Arjan F Theil Pierre-Olivier Mari Deborah Hoogstraten Jessica M Y Ng Christoffel Dinant Jan H J Hoeijmakers Wim Vermeulen
author_sort	Giuseppina Giglia-Mari
title	Dynamic interaction of TTDA with TFIIH is stabilized by nucleotide excision repair in living cells.
title_short	Dynamic interaction of TTDA with TFIIH is stabilized by nucleotide excision repair in living cells.
title_full	Dynamic interaction of TTDA with TFIIH is stabilized by nucleotide excision repair in living cells.
title_fullStr	Dynamic interaction of TTDA with TFIIH is stabilized by nucleotide excision repair in living cells.
title_full_unstemmed	Dynamic interaction of TTDA with TFIIH is stabilized by nucleotide excision repair in living cells.
title_sort	dynamic interaction of ttda with tfiih is stabilized by nucleotide excision repair in living cells.
publisher	Public Library of Science (PLoS)
publishDate	2006
url	https://doaj.org/article/9b5cec00a6f2471d8895e60b61883ddf
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Dynamic interaction of TTDA with TFIIH is stabilized by nucleotide excision repair in living cells.

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