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

doi:10.1038/s41467-018-03135-w

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)

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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 language	English
Article number	728
Pages (from-to)	1-11
Number of pages	11
Journal	Nature Communications
Volume	9
DOIs	https://doi.org/10.1038/s41467-018-03135-w
Publication status	Published - 20 Feb 2018

Keywords

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

ASJC Scopus subject areas

General Physics and Astronomy
General Chemistry
General Biochemistry,Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-018-03135-wLicence: CC BY

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Final published version, 5.5 MBLicence: CC BY

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.",

keywords = "Chromosome segregation, Cytokinesis, Caenorhabditis elegans/embryology, Animals, Mitosis, Chromatin/genetics, Endodeoxyribonucleases/genetics, DNA Replication, Caenorhabditis elegans Proteins/genetics, DNA/genetics",

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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doi = "10.1038/s41467-018-03135-w",

language = "English",

volume = "9",

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journal = "Nature Communications",

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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.

KW - Chromosome segregation

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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U2 - 10.1038/s41467-018-03135-w

DO - 10.1038/s41467-018-03135-w

M3 - Article

C2 - 29463814

SN - 2041-1723

VL - 9

SP - 1

EP - 11

JO - Nature Communications

JF - Nature Communications

M1 - 728

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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Functional Dissection of the Eukaryotic Replisome (Senior Investigator Award)

Dynamics of Fundamental Cellular Processes by Live Cell and Tissue Imaging

Gartner, Anton

Cite this

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

Functional Dissection of the Eukaryotic Replisome (Senior Investigator Award)

Dynamics of Fundamental Cellular Processes by Live Cell and Tissue Imaging

Profiles

Gartner, Anton

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