DNA repair is limiting for haematopoietic stem cells during ageing
Nijnik, Anastasia; Woodbine, Lisa; Marchetti, Caterina; Dawson, Sarah; Lambe, Teresa; Liu, Cong; Rodrigues, Neil P.; Crockford, Tanya; Cabuy, Erik; Vindigni, Alessandro; Enver, Tariq; Bell, John I; Slijepcevic, Predrag; Goodnow, Christopher; Jeggo, Penelope A.; Cornall, Richard J
Accumulation of DNA damage leading to adult stem cell exhaustion has been proposed to be a principal mechanism of ageing. Here we address this question by taking advantage of the highly specific role of DNA ligase IV in the repair of DNA double-strand breaks by non-homologous end-joining, and by the discovery of a unique mouse strain with a hypomorphic Lig4Y288C mutation. The Lig4Y288C mouse, identified by means of a mutagenesis screening programme, is a mouse model for human LIG4 syndrome,...[Show more]
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