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

P. Christopher Caridi, Laetitia Delabaere, Grzegorz Zapotoczny, Irene Chiolo*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

35 Scopus citations

Abstract

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 heterochromatic 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.

Original languageEnglish (US)
Article number20160291
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Volume372
Issue number1731
DOIs
StatePublished - 2017

Funding

Keywords

  • Drosophila
  • Genome stability
  • Heterochromatin repair
  • Homologous recombination
  • Nuclear architecture
  • Repeated DNA sequences

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences

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