And yet, it moves: nuclear and chromatin dynamics of a heterochromatic double-strand break

• Published in: Philosophical transactions of the Royal Society of London. Series B. Biological sciences 2017-10, Vol.372 (1731), p.1-14
• Main Authors: Caridi, P. Christopher, Delabaere, Laetitia, Zapotoczny, Grzegorz, Chiolo, Irene
• Format: Article
• Language: English
• ISSN: 0962-8436

Heterochromatin is mostly composed of repeated DNA sequences prone to aberrant recombination. How cells maintain the stability of these sequences during double-strand break (DSB) repair has been a long-standing mystery. Studies in Drosophila cells revealed that faithful homologous recombination repair of het erochromatic DSBs relies on the striking relocalization of repair sites to the nuclear periphery before Rad51 recruitment and repair progression. Here, we summarize our current understanding of this response, including the molecular mechanisms involved, and conserved pathways in mammalian cells. We will highlight important similarities with pathways identified in budding yeast for repair of other types of repeated sequences, including rDNA and short telomeres. We will also discuss the emerging role of chromatin composition and regulation in heterochromatin repair progression. Together, these discoveries challenged previous assumptions that repair sites are substantially static in multicellular eukaryotes, that heterochromatin is largely inert in the presence of DSBs, and that silencing and compaction in this domain are obstacles to repair. This article is part of the themed issue 'Chromatin modifiers and remodellers in DNA repair and signalling'.