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

Ye Hong, Remi Sonneville, Bin Wang, Viktor Scheidt, Bettina Meier, Alexander Woglar, Sarah Demetriou, Karim Labib, Verena Jantsch, Anton Gartner (Lead / Corresponding author)

Research output: Contribution to journalArticle

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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 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.

Original languageEnglish
Article number728
Pages (from-to)1-11
Number of pages11
JournalNature Communications
Volume9
DOIs
Publication statusPublished - 20 Feb 2018

Fingerprint

Lunar Module
nuclease
mitosis
chromatin
Deoxyribonucleases
Mitosis
Chromatin
Chromosomes
deoxyribonucleic acid
3'-nucleotidase
Genome
Genes
Aurora Kinase B
Chromosome Structures
genome
chromosomes
DNA
Chromosome Segregation
Cytokinesis
Homologous Recombination

Keywords

  • Chromosome segregation
  • Cytokinesis
  • Caenorhabditis elegans/embryology
  • Animals
  • Mitosis
  • Chromatin/genetics
  • Endodeoxyribonucleases/genetics
  • DNA Replication
  • Caenorhabditis elegans Proteins/genetics
  • DNA/genetics

Cite this

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title = "LEM-3 is a midbody-tethered DNA nuclease that resolves chromatin bridges during late mitosis",
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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author = "Ye Hong and Remi Sonneville and Bin Wang and Viktor Scheidt and Bettina Meier and Alexander Woglar and Sarah Demetriou and Karim Labib and Verena Jantsch and Anton Gartner",
note = "This work was funded by Wellcome Trust Programme (AG 0909444/Z/09/Z), Investigator (KL102943/Z/13/Z) and Strategic awards (097045/B/11/Z), a MRC core grant KL MC_UU_12016/13) and the FWF (VJ SFB-F34). VS and YH were supported by a Wellcome PhD fellowship and ISSF funds. The Dundee Imaging Facility was supported by the Wellcome Trust (097945/B/11/Z) and the MRC (MR/K015869/1).",
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month = "2",
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doi = "10.1038/s41467-018-03135-w",
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journal = "Nature Communications",
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LEM-3 is a midbody-tethered DNA nuclease that resolves chromatin bridges during late mitosis. / Hong, Ye; Sonneville, Remi; Wang, Bin; Scheidt, Viktor; Meier, Bettina; Woglar, Alexander; Demetriou, Sarah; Labib, Karim; Jantsch, Verena; Gartner, Anton (Lead / Corresponding author).

In: Nature Communications, Vol. 9, 728, 20.02.2018, p. 1-11.

Research output: Contribution to journalArticle

TY - JOUR

T1 - LEM-3 is a midbody-tethered DNA nuclease that resolves chromatin bridges during late mitosis

AU - Hong, Ye

AU - Sonneville, Remi

AU - Wang, Bin

AU - Scheidt, Viktor

AU - Meier, Bettina

AU - Woglar, Alexander

AU - Demetriou, Sarah

AU - Labib, Karim

AU - Jantsch, Verena

AU - Gartner, Anton

N1 - This work was funded by Wellcome Trust Programme (AG 0909444/Z/09/Z), Investigator (KL102943/Z/13/Z) and Strategic awards (097045/B/11/Z), a MRC core grant KL MC_UU_12016/13) and the FWF (VJ SFB-F34). VS and YH were supported by a Wellcome PhD fellowship and ISSF funds. The Dundee Imaging Facility was supported by the Wellcome Trust (097945/B/11/Z) and the MRC (MR/K015869/1).

PY - 2018/2/20

Y1 - 2018/2/20

N2 - 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.

AB - 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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KW - Cytokinesis

KW - Caenorhabditis elegans/embryology

KW - Animals

KW - Mitosis

KW - Chromatin/genetics

KW - Endodeoxyribonucleases/genetics

KW - DNA Replication

KW - Caenorhabditis elegans Proteins/genetics

KW - DNA/genetics

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DO - 10.1038/s41467-018-03135-w

M3 - Article

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VL - 9

SP - 1

EP - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

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