RRC ID 53960
Author Hong Y, Sonneville R, Wang B, Scheidt V, Meier B, Woglar A, Demetriou S, Labib K, Jantsch V, Gartner A.
Title LEM-3 is a midbody-tethered DNA nuclease that resolves chromatin bridges during late mitosis.
Journal Nat Commun
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.
Volume 9(1)
Pages 728
Published 2018-2-20
DOI 10.1038/s41467-018-03135-w
PII 10.1038/s41467-018-03135-w
PMID 29463814
PMC PMC5820297
MeSH 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*
IF 12.353
Resource
C.elegans tm3468