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

Nat Commun. 2018 Feb 20;9(1):728. doi: 10.1038/s41467-018-03135-w.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / enzymology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Cytokinesis
  • DNA / genetics
  • DNA / metabolism
  • DNA Replication
  • Endodeoxyribonucleases / genetics
  • Endodeoxyribonucleases / metabolism*
  • Mitosis*


  • Caenorhabditis elegans Proteins
  • Chromatin
  • DNA
  • Endodeoxyribonucleases
  • LEM-3 protein, C elegans