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bioRxiv · 10.1101/221291

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

HONG, Y.·Sonneville, R.·Wang, B.·Scheidt, V.·Meier, B.·Woglar, A.·Demetriou, S.·Labib, K.·Jantsch, V.·Gartner, A.
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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 new 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 act 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.

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HONG, Y., Sonneville, R., Wang, B., Scheidt, V., Meier, B., Woglar, A., Demetriou, S., Labib, K., Jantsch, V., Gartner, A.. 2017-11-17. LEM-3 is a midbody-tethered DNA nuclease that resolves chromatin bridges during cytokinesis. https://doi.org/10.1101/221291

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