ATRX dysfunction Induces replication defects in primary mouse cells

Clynes, David, Jelinska, Clare, Xella, Barbara , Ayyub, Helena, Taylor, Stephen, Mitson, Matthew, Bachrati, Csanad, Higgs, Douglas R. and Gibbons, Richard J. (2014) ATRX dysfunction Induces replication defects in primary mouse cells. PLoS ONE, 9 (3). e92915. ISSN 1932-6203

Full content URL: http://dx.doi.org/10.1371/journal.pone.0092915

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ATRX Dysfunction Induces Replication Defects in Primary Mouse Cells
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Abstract

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.

Keywords:DNA replication, Telomere maintenance, ATRX, G quadruplex, Alternative lengthening of telomeres, JCOpen
Subjects:C Biological Sciences > C700 Molecular Biology, Biophysics and Biochemistry
Divisions:College of Science > School of Life Sciences
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ID Code:14466
Deposited On:11 Nov 2014 10:29

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