The response to DNA damage in heterochromatin domains

Abstract

Eukaryotic genomes are organized into chromatin, divided into structurally and functionally distinct euchromatin and heterochromatin compartments. The high level of compaction and the abundance of repeated sequences in heterochromatin pose multiple challenges for the maintenance of genome stability. Cells have evolved sophisticated and highly controlled mechanisms to overcome these constraints. Here, we summarize recent findings on how the heterochromatic state influences DNA damage formation, signaling, and repair. By focusing on distinct heterochromatin domains in different eukaryotic species, we highlight the heterochromatin contribution to the compartmentalization of DNA damage repair in the cell nucleus and to the repair pathway choice. We also describe the diverse chromatin alterations associated with the DNA damage response in heterochromatin domains and present our current understanding of their regulatory mechanisms. Finally, we discuss the biological significance and the evolutionary conservation of these processes.

A cohesin/HUSH- and LINC-dependent pathway controls ribosomal DNA double-strand break repair

“…Fourth, we reported previously that both the actin network and the LINC complex contribute to clustering of DSBs induced in active genes in G1 (Aymard et al 2017). Of importance all of the abovementioned DSBs were described previously as refractory to fast repair (for review, see Marnef et al 2017;Fortuny and Polo 2018). We thus propose that breaks in rDNA may also display impaired or delayed repair kineticsin line with its repetitive nature, high RNA Pol I occupancy, and prevalence of secondary structures (R loops and G4)-and hence use similar mobilization pathways to undergo safe repair.…”

Studying DNA Double-Strand Break Repair: An Ever-Growing Toolbox

“…In addition, during DSB repair, the destabilization of nucleosomes further enhances accessibility and regulate the mobility of the broken DNA ends (Clouaire and Legube, 2019). Moreover, the original chromatin landscape of the damaged locus also contributes to the decision between DSB repair pathways (Clouaire and Legube, 2015;Fortuny and Polo, 2018;Bartke and Groth, 2019).…”

Job Opening for Nucleosome Mechanic: Flexibility Required

“…One could hypothesize that heterochromatin, which has increased local contacts with the nuclear periphery, may have a better buffering capacity to dissipate shearing forces. Indeed, evidence supports this notion, because DNA damage commonly correlates with local decondensed or relaxed chromatin [52,53], although some heterochromatin domains do not decondense upon DNA damage [54]. Concurrently, it will be fascinating to study how species which lack heterochromatin factors [55] adapt to shearing forces.…”