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Trends Genet. 2017 Feb;33(2):86-100. doi: 10.1016/j.tig.2016.12.004. Epub 2017 Jan 16.

Nuclear Dynamics of Heterochromatin Repair.

Author information

1
University of Southern California, Molecular and Computational Biology Department, Los Angeles, CA 90089, USA.
2
University of Southern California, Molecular and Computational Biology Department, Los Angeles, CA 90089, USA. Electronic address: chiolo@usc.edu.

Abstract

Repairing double-strand breaks (DSBs) is particularly challenging in pericentromeric heterochromatin, where the abundance of repeated sequences exacerbates the risk of ectopic recombination and chromosome rearrangements. Recent studies in Drosophila cells revealed that faithful homologous recombination (HR) repair of heterochromatic DSBs relies on the relocalization of DSBs to the nuclear periphery before Rad51 recruitment. We summarize here the exciting progress in understanding this pathway, including conserved responses in mammalian cells and surprising similarities with mechanisms in yeast that deal with DSBs in distinct sites that are difficult to repair, including other repeated sequences. We will also point out some of the most important open questions in the field and emerging evidence suggesting that deregulating these pathways might have dramatic consequences for human health.

PMID:
28104289
PMCID:
PMC5285325
DOI:
10.1016/j.tig.2016.12.004
[Indexed for MEDLINE]
Free PMC Article

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