Titel
LEM-3 is a midbody-tethered DNA nuclease that resolves chromatin bridges during late mitosis
Autor*in
Ye Hong
Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee
Remi Sonneville
MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee
Bin Wang
Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee
... show all
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.
Stichwort
Chromosome segregationCytokinesis
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
Erschienen in
Titel
Nature Communications
Band
9
Publication
Springer Science and Business Media LLC
Erscheinungsdatum
2018
Zugänglichkeit
Rechte
Rechteangabe
© The Author(s) 2018
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