Assembling nuclear domains: Lessons from DNA repair

Abstract

Eukaryotic nuclei are organized into nuclear domains that unite loci sharing a common function. These domains are essential for diverse processes including (1) the formation of topologically associated domains (TADs) that coordinate replication and transcription, (2) the formation of specialized transcription and splicing factories, and (3) the clustering of DNA double-strand breaks (DSBs), which concentrates damaged DNA for repair. The generation of nuclear domains requires forces that are beginning to be identified. In the case of DNA DSBs, DNA movement and clustering are driven by actin filament nucleators. Furthermore, RNAs and low-complexity protein domains such as RNA-binding proteins also accumulate around sites of transcription and repair. The link between liquid–liquid phase separation and actin nucleation in the formation of nuclear domains is still unknown. This review discusses DSB repair domain formation as a model for functional nuclear domains in other genomic contexts.

The methylation status of the embryonic limb skeletal progenitors determines their cell fate in chicken

“…In this regard, it is remarkable that irradiation, that is an unspecific, and potent, genotoxic agent, induces a wider distribution of γH2AX marks, that differs from its preferential distribution in the contour of 5mC marks during physiological degeneration. This finding is consistent with the organization of chromatin in dynamic domains of distinct functional significance 52 . Remarkably, SOX9 appears to be a key factor in the establishment of functional chromatin domains 54 , and it may play a central role in the control of cell death in the embryonic limbs 55,56 .…”

“…Among the potential factors that methylation might induce in skeletal progenitors are active changes in nuclear chromatin domains 52 . It is now well established that the regulation of 5mC patterns in embryonic cells is of major importance in the control of cell differentiation (reviewed by ref.…”

Formation of adenovirus DNA replication compartments

“…The cell nucleus is organized in discrete compartments—termed nuclear bodies (NB) or nuclear domains (ND). Some NB—such as nucleoli, Cajal bodies (CB), or Tumor suppressor p53‐binding protein 1 (53BP1)‐marked repair compartments—are known to form through liquid–liquid phase separation (LLPS) and all are linked to regulation of nuclear activities, including genome replication , gene transcription , post‐transcriptional RNA processing , ribosome assembly , spliceosome assembly , chromatin remodeling , and DNA repair , allowing proper control of gene expression, as well as genome and cellular homeostasis maintenance .…”

Meiotic Chromosome Contacts as a Plausible Prelude for Robertsonian Translocations

“…The combined variant of both models was also proposed. If DSBs occur in G1 and are not repaired until G2, they may cluster and form translocations [30].…”