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1. ATRX dysfunction induces replication defects in primary mouse cells.

Author

David Clynes, Clare Jelinska, Barbara Xella, Helena Ayyub, Stephen Taylor, Matthew Mitson, Csanád Z Bachrati, Douglas R Higgs, and Richard J Gibbons

Subjects
Medicine, Science
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.

Published
2014
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2. ATRX dysfunction induces replication defects in primary mouse cells

Author

Richard J. Gibbons, Stephen Taylor, David Clynes, Matthew Mitson, Clare Jelinska, Csanád Z. Bachrati, Barbara Xella, Helena Ayyub, and Douglas R. Higgs

Subjects
DNA Replication, Chromosome Structure and Function, X-linked Nuclear Protein, Telomerase, Forms of DNA, DNA damage, Telomere Pathway, DNA repair, lcsh:Medicine, Biology, Biochemistry, Chromosomes, Chromatin remodeling, Cell Line, S Phase, Gene Knockout Techniques, Mice, Nucleic Acids, Genetics, Animals, Humans, DNA Breaks, Double-Stranded, lcsh:Science, Embryonic Stem Cells, ATRX, Multidisciplinary, Biology and life sciences, Chromosome Biology, lcsh:R, DNA Helicases, DNA replication, Nuclear Proteins, DNA, Cell Biology, Telomere, Chromatin Assembly and Disassembly, Chromatin, Cell biology, Telomeres, Multiprotein Complexes, C700 Molecular Biology, Biophysics and Biochemistry, Epigenetics, lcsh:Q, Gene Function, Homologous recombination, Research Article, DNA Damage
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.

Published
2014

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