Abstract
The eukaryotic nucleus is continuously being exposed to endogenous and exogenous sources that cause DNA breaks, whose faithful repair requires the activity of dedicated nuclear machineries. DNA is packaged into a variety of chromatin domains, each characterized by specific molecular properties that regulate gene expression and help maintain nuclear structure. These different chromatin environments each demand a tailored response to DNA damage. Silenced chromatin domains in particular present a major challenge to the cell’s DNA repair machinery due to their specific biophysical properties and distinct, often repetitive, DNA content. To this end, we here discuss the interplay between silenced chromatin domains and DNA damage repair, specifically double-strand breaks, and how these processes help maintain genome stability.
Highlights
An essential condition for organismal life is the ability to maintain an intact genome
We will predominantly focus on repair mechanisms in pericentromeric heterochromatin and will highlight several studies performed in other silenced regions, such as lamina-associated domains or facultative heterochromatin
One hint for its specific role in heterochromatin repair comes from the fact that the SUMOylation activity of Drosophila Quijote and Cervantes is important to target and retain heterochromatic double-strand break (DSB) at the nuclear periphery [20,87]. This peripheral retention of heterochromatic DSBs depends on the presence of small ubiquitin-like modifier (SUMO) Targeted Ubiquitin Ligases (STUbL), which are enriched at the nuclear periphery
Summary
An essential condition for organismal life is the ability to maintain an intact genome. Regions of constitutive heterochromatin require striking movements of the DSB to the periphery of the heterochromatin domain or the nuclear periphery to repair the damage [19,20,21,22,23] These studies highlight the importance of acquiring unique DSB repair responses in different chromatin regions. Silenced chromatin regions, such as pericentromeric heterochromatin, present a particular challenge to the cell’s repair machinery Do these domains possess compact, phase-separated structures [24,25,26,27,28] that demand local chromatin changes to access and repair the breaks, their DNA often consists of thousands of repetitive sequences (reviewed in [29]), which necessitates a coordinated repair response to prevent aberrant recombination between these repeats. We will predominantly focus on repair mechanisms in pericentromeric heterochromatin and will highlight several studies performed in other silenced regions, such as lamina-associated domains or facultative heterochromatin
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