LEM-3 is a midbody-tethered DNA nuclease that resolves chromatin bridges during late mitosis

Ye Hong, Remi Sonneville, Bin Wang, Viktor Scheidt, Bettina Meier, Alexander Woglar, Sarah Demetriou, Karim Labib, Verena Jantsch, Anton Gartner (Lead / Corresponding author)

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Abstract

Faithful chromosome segregation and genome maintenance requires the removal of all DNA bridges that physically link chromosomes before cells divide. Using C. elegans embryos we show that the LEM-3/Ankle1 nuclease defines a previously undescribed genome integrity mechanism by processing DNA bridges right before cells divide. LEM-3 acts at the midbody, the structure where abscission occurs at the end of cytokinesis. LEM-3 localization depends on factors needed for midbody assembly, and LEM-3 accumulation is increased and prolonged when chromatin bridges are trapped at the cleavage plane. LEM-3 locally processes chromatin bridges that arise from incomplete DNA replication, unresolved recombination intermediates, or the perturbance of chromosome structure. Proper LEM-3 midbody localization and function is regulated by AIR-2/Aurora B kinase. Strikingly, LEM-3 acts cooperatively with the BRC-1/BRCA1 homologous recombination factor to promote genome integrity. These findings provide a molecular basis for the suspected role of the LEM-3 orthologue Ankle1 in human breast cancer.

Original languageEnglish
Article number728
Pages (from-to)1-11
Number of pages11
JournalNature Communications
Volume9
DOIs
Publication statusPublished - 20 Feb 2018

Keywords

  • Chromosome segregation
  • Cytokinesis
  • Caenorhabditis elegans/embryology
  • Animals
  • Mitosis
  • Chromatin/genetics
  • Endodeoxyribonucleases/genetics
  • DNA Replication
  • Caenorhabditis elegans Proteins/genetics
  • DNA/genetics

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