当前位置： SCI文献检索 > MOLECULAR BIOLOGY OF THE CELL期刊下所有文献 > The Werner syndrome protein is involved in RNA polymerase II transcription.

The Werner syndrome protein is involved in RNA polymerase II transcription.

Abstract：

:Werner syndrome (WS) is a human progeroid syndrome characterized by the early onset of a large number of clinical features associated with the normal aging process. The complex molecular and cellular phenotypes of WS involve characteristic features of genomic instability and accelerated replicative senescence. The gene involved (WRN) was recently cloned, and its gene product (WRNp) was biochemically characterized as a helicase. Helicases play important roles in a variety of DNA transactions, including DNA replication, transcription, repair, and recombination. We have assessed the role of the WRN gene in transcription by analyzing the efficiency of basal transcription in WS lymphoblastoid cell lines that carry homozygous WRN mutations. Transcription was measured in permeabilized cells by [3H]UTP incorporation and in vitro by using a plasmid template containing the RNA polymerase II (RNA pol II)-dependent adenovirus major late promoter. With both of these approaches, we find that the transcription efficiency in different WS cell lines is reduced to 40-60% of the transcription in cells from normal individuals. This defect can be complemented by the addition of normal cell extracts to the chromatin of WS cells. Addition of purified wild-type WRNp but not mutated WRNp to the in vitro transcription assay markedly stimulates RNA pol II-dependent transcription carried out by nuclear extracts. A nonhelicase domain (a direct repeat of 27 amino acids) also appears to have a role in transcription enhancement, as revealed by a yeast hybrid-protein reporter assay. This is further supported by the lack of stimulation of transcription when mutant WRNp lacking this domain was added to the in vitro assay. We have thus used several approaches to show a role for WRNp in RNA pol II transcription, possibly as a transcriptional activator. A deficit in either global or regional transcription in WS cells may be a primary molecular defect responsible for the WS clinical phenotype.

journal_name

Mol Biol Cell

journal_title

Molecular biology of the cell

authors

Balajee AS,Machwe A,May A,Gray MD,Oshima J,Martin GM,Nehlin JO,Brosh R,Orren DK,Bohr VA

doi

10.1091/mbc.10.8.2655

keywords:

subject

Has Abstract

pub_date

1999-08-01 00:00:00

pages

2655-68

issue

eissn

1059-1524

issn

1939-4586

journal_volume

pub_type

杂志文章

在线工具

The Werner syndrome protein is involved in RNA polymerase II transcription.