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

Nature Communications
Ye HongAnton Gartner

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.

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Citations

Sep 27, 2018·Cell Cycle·Ying Wai Chan, Stephen C West
Sep 12, 2019·International Journal of Cancer. Journal International Du Cancer·Jianbo TianXiaoping Miao
Sep 5, 2020·PLoS Genetics·Jeremy A HollisDiana E Libuda
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Jul 16, 2019·Cellular and Molecular Life Sciences : CMLS·Eleni Petsalaki, George Zachos
Aug 21, 2020·Journal of Cell Science·Rhiannon M Sears, Kyle J Roux
Oct 17, 2020·The Journal of Cell Biology·Brennan M DanlaskyFrancis J McNally
Jun 1, 2021·Frontiers in Cell and Developmental Biology·Ye HongAnton Gartner
Jun 30, 2021·Current Opinion in Genetics & Development·Ondrej BelanSimon J Boulton

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Methods Mentioned

BETA
super-resolution microscopy
dissection
PCR

Software Mentioned

MetaMorph
ImageJ

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