ATRX dysfunction induces replication defects in primary mouse cells

The chromatin remodeling protein ATRX, which targets tandem repetitive DNA, has been shown to be required for expression of the alpha globin genes, for proliferation of a variety of cellular progenitors, for chromosome congression and for the maintenance of telomeres. Mutations in ATRX have recently...

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Hlavní autoři: Clynes, D, Jelinska, C, Xella, B, Ayyub, H, Taylor, S, Mitson, M, Bachrati, C, Higgs, D, Gibbons, R
Médium: Journal article
Jazyk:English
Vydáno: Public Library of Science 2014
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author Clynes, D
Jelinska, C
Xella, B
Ayyub, H
Taylor, S
Mitson, M
Bachrati, C
Higgs, D
Gibbons, R
author_facet Clynes, D
Jelinska, C
Xella, B
Ayyub, H
Taylor, S
Mitson, M
Bachrati, C
Higgs, D
Gibbons, R
author_sort Clynes, D
collection OXFORD
description The chromatin remodeling protein ATRX, which targets tandem repetitive DNA, has been shown to be required for expression of the alpha globin genes, for proliferation of a variety of cellular progenitors, for chromosome congression and for the maintenance of telomeres. Mutations in ATRX have recently been identified in tumours which maintain their telomeres by a telomerase independent pathway involving homologous recombination thought to be triggered by DNA damage. It is as yet unknown whether there is a central underlying mechanism associated with ATRX dysfunction which can explain the numerous cellular phenomena observed. There is, however, growing evidence for its role in the replication of various repetitive DNA templates which are thought to have a propensity to form secondary structures. Using a mouse knockout model we demonstrate that ATRX plays a direct role in facilitating DNA replication. Ablation of ATRX alone, although leading to a DNA damage response at telomeres, is not sufficient to trigger the alternative lengthening of telomere pathway in mouse embryonic stem cells.
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spelling oxford-uuid:b3667104-2f6c-4772-be1e-48e9a28cfdde2022-03-27T04:18:47ZATRX dysfunction induces replication defects in primary mouse cellsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b3667104-2f6c-4772-be1e-48e9a28cfddeEnglishSymplectic Elements at OxfordPublic Library of Science2014Clynes, DJelinska, CXella, BAyyub, HTaylor, SMitson, MBachrati, CHiggs, DGibbons, RThe chromatin remodeling protein ATRX, which targets tandem repetitive DNA, has been shown to be required for expression of the alpha globin genes, for proliferation of a variety of cellular progenitors, for chromosome congression and for the maintenance of telomeres. Mutations in ATRX have recently been identified in tumours which maintain their telomeres by a telomerase independent pathway involving homologous recombination thought to be triggered by DNA damage. It is as yet unknown whether there is a central underlying mechanism associated with ATRX dysfunction which can explain the numerous cellular phenomena observed. There is, however, growing evidence for its role in the replication of various repetitive DNA templates which are thought to have a propensity to form secondary structures. Using a mouse knockout model we demonstrate that ATRX plays a direct role in facilitating DNA replication. Ablation of ATRX alone, although leading to a DNA damage response at telomeres, is not sufficient to trigger the alternative lengthening of telomere pathway in mouse embryonic stem cells.
spellingShingle Clynes, D
Jelinska, C
Xella, B
Ayyub, H
Taylor, S
Mitson, M
Bachrati, C
Higgs, D
Gibbons, R
ATRX dysfunction induces replication defects in primary mouse cells
title ATRX dysfunction induces replication defects in primary mouse cells
title_full ATRX dysfunction induces replication defects in primary mouse cells
title_fullStr ATRX dysfunction induces replication defects in primary mouse cells
title_full_unstemmed ATRX dysfunction induces replication defects in primary mouse cells
title_short ATRX dysfunction induces replication defects in primary mouse cells
title_sort atrx dysfunction induces replication defects in primary mouse cells
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