Ageing-related chromatin defects through loss of the NURD complex

G Pegoraro, N Kubben, U Wickert, H Göhler… - Nature cell …, 2009 - nature.com
G Pegoraro, N Kubben, U Wickert, H Göhler, K Hoffmann, T Misteli
Nature cell biology, 2009nature.com
Physiological and premature ageing are characterized by multiple defects in chromatin
structure and accumulation of persistent DNA damage. Here we identify the NURD
chromatin remodelling complex as a key modulator of these ageing-associated chromatin
defects. We demonstrate loss of several NURD components during premature and normal
ageing and we find an ageing-associated reduction in HDAC1 activity. Silencing of
individual NURD subunits recapitulated chromatin defects associated with ageing and we …
Abstract
Physiological and premature ageing are characterized by multiple defects in chromatin structure and accumulation of persistent DNA damage. Here we identify the NURD chromatin remodelling complex as a key modulator of these ageing-associated chromatin defects. We demonstrate loss of several NURD components during premature and normal ageing and we find an ageing-associated reduction in HDAC1 activity. Silencing of individual NURD subunits recapitulated chromatin defects associated with ageing and we provide evidence that structural chromatin defects precede DNA damage accumulation. These results outline a molecular mechanism for chromatin defects during ageing.
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