Histone modification by reversible lysine acetylation is a key regulatory mechanism in chromatin and nuclear signaling, whose deregulation is linked to aging, cancer, and other diseases. New work by Vazquez et al (2016) uncovers a role for the sirtuin family deacetylase SIRT7, which controls epigenetic maintenance of oncogenic gene expression programs, mitochondrial homeostasis, and ribosome biogenesis, in promoting genomic stability and DNA repair via site‐specific deacetylation of a damage‐associated histone mark, H3K18Ac.
See also: BN Vazquez et al
DNA is susceptible to damage from both environmental agents and cell intrinsic sources, and unrepaired or misrepaired damage is implicated in aging‐related pathology and cancer. DNA double‐strand breaks (DSBs) are particularly dangerous lesions. Defects in their repair can lead to mutations, DNA rearrangements, cell death, or senescence. The major DSB repair pathways in mammalian cells are non‐homologous end joining (NHEJ) and homologous recombination‐mediated repair (HR). Both pathways involve factors that detect damage, determine repair pathway choice, or activate downstream signaling (Smeenk & van Attikum, 2013). There is growing appreciation that chromatin regulation at sites of DNA damage plays pivotal roles in DNA repair and damage signaling. Changes in post‐translational histone modifications—such as phosphorylation, acetylation, or methylation—at DSBs can increase chromatin accessibility or provide docking sites for damage signaling or repair factors. Thus, complex networks of interactions involving histone marks, their modifying enzymes, and downstream modification readers contribute to dynamic chromatin changes that are necessary for recognition and repair of damaged DNA (Smeenk & van Attikum, 2013).
SIRT7 is a member of the sirtuin family of NAD+‐dependent lysine deacetylase enzymes, which play diverse roles in aging, metabolism, and disease processes (Chalkiadaki & Guarente, 2015). Studies over the past 5 years have identified roles for SIRT7 in regulating epigenetic and cellular homeostasis through deacetylation of histones and other nuclear proteins (Fig 1B). In chromatin, SIRT7 …
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