The University of Southampton
University of Southampton Institutional Repository

Phenotypic heterogeneity in the XPB DNA helicase gene (ERCC3): xeroderma pigmentosum without and with Cockayne syndrome

Oh, Kyu-Seon, Khan, Sikandar G., Jaspers, N.G.J., Raams, Anja, Ueda, Takahiro, Lehmann, Alan, Friedmann, Peter S., Emmert, Steffen, Gratchev, Alexi, Lachlan, Katherine, Lucassen, Anneke, Baker, Carl C. and Kraemer, Kenneth H. (2006) Phenotypic heterogeneity in the XPB DNA helicase gene (ERCC3): xeroderma pigmentosum without and with Cockayne syndrome Human Mutation, 27, (11), pp. 1092-1103. (doi:10.1002/humu.20392).

Record type: Article

Abstract

Defects in the xeroderma pigmentosum type B (XPB) gene (ERCC3), a DNA helicase involved in nucleotide excision repair (NER) and an essential subunit of the basal transcription factor, TFIIH, have been described in only three families. We report three new XPB families: one has two sisters with relatively mild xeroderma pigmentosum (XP) symptoms not previously associated with XPB mutations and two have severe XP/Cockayne syndrome (CS) complex symptoms. All XP-B cells had reduced NER and post-ultraviolet (UV) cell viability. Surprisingly, cells from the milder XP sisters had the same missense mutation (c.296T>C, p.F99S) that was previously reported in two mild XP/CS complex brothers. These cells had higher levels of XPB protein than the severely affected XP/CS complex patients. An XPB expression vector with the p.F99S mutation partially complemented the NER defect in XP-B cells. The three severely affected XP/CS complex families all have the same splice acceptor site mutation (c.2218-6C>A, p.Q739insX42) in one allele. This resulted in alteration of 41 amino acids at the C terminus, producing partial NER complementation. This limited number of mutations probably reflects the very restricted range of alterations of this vital protein that are compatible with life. We found new mutations in the second allele yielding markedly truncated proteins in all five XP or XP/CS complex families: c.1273C>T, p.R425X; c.471+1G>A, p.K157insTSDSX; c.807-808delTT, p.F270X; c.1421-1422insA, p.D474EfsX475; and c.1633C>T, p.Q545X. The remarkable phenotypic heterogeneity of XPB is associated with partially active missense mutations in milder patients while severe XP/CS complex patients have nonsense mutations in both alleles with low levels of altered XPB proteins.

Full text not available from this repository.

More information

Published date: 2006
Keywords: DNA repair, TFIIH, transcription, neurodegeneration, skin cancer, XPB, ERCC3

Identifiers

Local EPrints ID: 44279
URI: http://eprints.soton.ac.uk/id/eprint/44279
ISSN: 1059-7794
PURE UUID: d3455cbb-658c-4279-840c-5f7f394f56cd

Catalogue record

Date deposited: 22 Feb 2007
Last modified: 17 Jul 2017 15:15

Export record

Altmetrics

Contributors

Author: Kyu-Seon Oh
Author: Sikandar G. Khan
Author: N.G.J. Jaspers
Author: Anja Raams
Author: Takahiro Ueda
Author: Alan Lehmann
Author: Peter S. Friedmann
Author: Steffen Emmert
Author: Alexi Gratchev
Author: Katherine Lachlan
Author: Anneke Lucassen
Author: Carl C. Baker
Author: Kenneth H. Kraemer

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×