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Article ; Online: Modeling specific aneuploidies: from karyotype manipulations to biological insights.

Truong, My Anh / Cané-Gasull, Paula / Lens, Susanne M A

Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology

2023 Volume 31, Issue 3, Page(s) 25

Abstract: An abnormal chromosome number, or aneuploidy, underlies developmental disorders and is a common feature of cancer, with different cancer types exhibiting distinct patterns of chromosomal gains and losses. To understand how specific aneuploidies emerge in ...

Abstract	An abnormal chromosome number, or aneuploidy, underlies developmental disorders and is a common feature of cancer, with different cancer types exhibiting distinct patterns of chromosomal gains and losses. To understand how specific aneuploidies emerge in certain tissues and how they contribute to disease development, various methods have been developed to alter the karyotype of mammalian cells and mice. In this review, we provide an overview of both classic and novel strategies for inducing or selecting specific chromosomal gains and losses in human and murine cell systems. We highlight how these customized aneuploidy models helped expanding our knowledge of the consequences of specific aneuploidies to (cancer) cell physiology.
MeSH term(s)	Humans ; Animals ; Mice ; Karyotyping ; Karyotype ; Aneuploidy ; Chromosome Aberrations ; Mammals
Language	English
Publishing date	2023-08-29
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1161632-5
ISSN	1573-6849 ; 0967-3849
ISSN (online)	1573-6849
ISSN	0967-3849
DOI	10.1007/s10577-023-09735-7
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Article ; Online: Leave no sister behind.

Hadders, Michael A / Lens, Susanne M A

Cell reports

2021 Volume 37, Issue 7, Page(s) 110053

Abstract: Recent work published in Cell Reports and Developmental Cell from Sen et al., Orr et al., and Papini et al., demonstrates that midzone-based Aurora B resolves chromosome segregation errors during anaphase. ...

Abstract	Recent work published in Cell Reports and Developmental Cell from Sen et al., Orr et al., and Papini et al., demonstrates that midzone-based Aurora B resolves chromosome segregation errors during anaphase.
MeSH term(s)	Anaphase ; Aurora Kinase B ; Chromosome Segregation
Chemical Substances	Aurora Kinase B (EC 2.7.11.1)
Language	English
Publishing date	2021-11-17
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2021.110053
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Article ; Online: Delaying the final cut: A close encounter of checkpoint kinases at the midbody.

Hadders, Michael A / Lens, Susanne M A

The Journal of cell biology

2021 Volume 220, Issue 2

Abstract: How chromatin bridges are relayed to the chromosomal passenger complex (CPC) during mammalian cell division is unknown. In this issue, Petsalaki and Zachos (2020. J. Cell Biol.https://doi.org/10.1083/jcb.202008029) show that the DNA damage checkpoint ... ...

Abstract	How chromatin bridges are relayed to the chromosomal passenger complex (CPC) during mammalian cell division is unknown. In this issue, Petsalaki and Zachos (2020. J. Cell Biol.https://doi.org/10.1083/jcb.202008029) show that the DNA damage checkpoint kinases ATM and Chk2 signal to the CPC to associate with a pool of cytoskeletal regulators, MKLP2-Cep55, in the midbody center and to delay abscission.
MeSH term(s)	Animals ; Aurora Kinase B/genetics ; Cell Cycle Proteins/genetics ; Cell Division ; Cytokinesis ; HeLa Cells ; Humans ; Spindle Apparatus
Chemical Substances	Cell Cycle Proteins ; Cep55 protein, human ; Aurora Kinase B (EC 2.7.11.1)
Language	English
Publishing date	2021-01-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	218154-x
ISSN	1540-8140 ; 0021-9525
ISSN (online)	1540-8140
ISSN	0021-9525
DOI	10.1083/jcb.202012130
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Article ; Online: Changing places: Chromosomal Passenger Complex relocation in early anaphase.

Hadders, Michael A / Lens, Susanne M A

Trends in cell biology

2021 Volume 32, Issue 2, Page(s) 165–176

Abstract: The Chromosomal Passenger Complex (CPC) regulates a plethora of processes during multiple stages of nuclear and cytoplasmic division. Early during mitosis, the CPC is recruited to centromeres and kinetochores, and ensures that the duplicated chromosomes ... ...

Abstract	The Chromosomal Passenger Complex (CPC) regulates a plethora of processes during multiple stages of nuclear and cytoplasmic division. Early during mitosis, the CPC is recruited to centromeres and kinetochores, and ensures that the duplicated chromosomes become properly connected to microtubules from opposite poles of the mitotic spindle. Progression into anaphase is accompanied by a striking relocation of the CPC from centromeres to the antiparallel microtubule overlaps of the anaphase spindle and to the equatorial cortex. This translocation requires direct interactions of the CPC with the kinesin-6 family member MKLP2/KIF20A, and the inactivation of cyclin B-cyclin-dependent kinase-1 (CDK1). Here, we review recent progress in the regulation of this relocation event. Furthermore, we discuss why the CPC must be relocated during early anaphase in light of recent advances in the functions of the CPC post metaphase.
MeSH term(s)	Anaphase ; Aurora Kinase B/genetics ; Centromere ; Chromosomal Proteins, Non-Histone ; Humans ; Microtubules ; Mitosis ; Spindle Apparatus
Chemical Substances	Chromosomal Proteins, Non-Histone ; Aurora Kinase B (EC 2.7.11.1)
Language	English
Publishing date	2021-10-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	30122-x
ISSN	1879-3088 ; 0962-8924
ISSN (online)	1879-3088
ISSN	0962-8924
DOI	10.1016/j.tcb.2021.09.008
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Article ; Online: Leave no sister behind

Michael A. Hadders / Susanne M.A. Lens

Cell Reports, Vol 37, Iss 7, Pp 110053- (2021)

2021

Abstract	Recent work published in Cell Reports and Developmental Cell from Sen et al., Orr et al., and Papini et al., demonstrates that midzone-based Aurora B resolves chromosome segregation errors during anaphase.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: Cytokinesis defects and cancer.

Lens, Susanne M A / Medema, René H

Nature reviews. Cancer

2018 Volume 19, Issue 1, Page(s) 32–45

Abstract: Whole-genome and centrosome duplication as a consequence of cytokinesis failure can drive tumorigenesis in experimental model systems. However, whether cytokinesis failure is in fact an important cause of human cancers has remained unclear. In this ... ...

Abstract	Whole-genome and centrosome duplication as a consequence of cytokinesis failure can drive tumorigenesis in experimental model systems. However, whether cytokinesis failure is in fact an important cause of human cancers has remained unclear. In this Review, we summarize evidence that whole-genome-doubling events are frequently observed in human cancers and discuss the contribution that cytokinesis defects can make to tumorigenesis. We provide an overview of the potential causes of cytokinesis failure and discuss how tetraploid cells that are generated through cytokinesis defects are used in cancer as a transitory state on the route to aneuploidy. Finally, we discuss how cytokinesis defects can facilitate genetic diversification within the tumour to promote cancer development and could constitute the path of least resistance in tumour evolution.
MeSH term(s)	Aneuploidy ; Animals ; Carcinogenesis/genetics ; Carcinogenesis/pathology ; Centrosome/pathology ; Cytokinesis/genetics ; Genome/genetics ; Humans ; Neoplasms/genetics ; Neoplasms/pathology
Language	English
Publishing date	2018-12-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2062767-1
ISSN	1474-1768 ; 1474-175X
ISSN (online)	1474-1768
ISSN	1474-175X
DOI	10.1038/s41568-018-0084-6
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Zs.A 5563: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: The Ins and Outs of Aurora B Inner Centromere Localization.

Hindriksen, Sanne / Lens, Susanne M A / Hadders, Michael A

Frontiers in cell and developmental biology

2017 Volume 5, Page(s) 112

Abstract: Error-free chromosome segregation is essential for the maintenance of genomic integrity during cell division. Aurora B, the enzymatic subunit of the Chromosomal Passenger Complex (CPC), plays a crucial role in this process. In early mitosis Aurora B ... ...

Abstract	Error-free chromosome segregation is essential for the maintenance of genomic integrity during cell division. Aurora B, the enzymatic subunit of the Chromosomal Passenger Complex (CPC), plays a crucial role in this process. In early mitosis Aurora B localizes predominantly to the inner centromere, a specialized region of chromatin that lies at the crossroads between the inter-kinetochore and inter-sister chromatid axes. Two evolutionarily conserved histone kinases, Haspin and Bub1, control the positioning of the CPC at the inner centromere and this location is thought to be crucial for the CPC to function. However, recent studies sketch a subtler picture, in which not all functions of the CPC require strict confinement to the inner centromere. In this review we discuss the molecular pathways that direct Aurora B to the inner centromere and deliberate if and why this specific localization is important for Aurora B function.
Language	English
Publishing date	2017-12-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2017.00112
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Article ; Online: PLK1 plays dual roles in centralspindlin regulation during cytokinesis.

Adriaans, Ingrid E / Basant, Angika / Ponsioen, Bas / Glotzer, Michael / Lens, Susanne M A

The Journal of cell biology

2019 Volume 218, Issue 4, Page(s) 1250–1264

Abstract: Cytokinesis begins upon anaphase onset. An early step involves local activation of the small GTPase RhoA, which triggers assembly of an actomyosin-based contractile ring at the equatorial cortex. Here, we delineated the contributions of PLK1 and Aurora B ...

Abstract	Cytokinesis begins upon anaphase onset. An early step involves local activation of the small GTPase RhoA, which triggers assembly of an actomyosin-based contractile ring at the equatorial cortex. Here, we delineated the contributions of PLK1 and Aurora B to RhoA activation and cytokinesis initiation in human cells. Knock-down of PRC1, which disrupts the spindle midzone, revealed the existence of two pathways that can initiate cleavage furrow ingression. One pathway depends on a well-organized spindle midzone and PLK1, while the other depends on Aurora B activity and centralspindlin at the equatorial cortex and can operate independently of PLK1. We further show that PLK1 inhibition sequesters centralspindlin onto the spindle midzone, making it unavailable for Aurora B at the equatorial cortex. We propose that PLK1 activity promotes the release of centralspindlin from the spindle midzone through inhibition of PRC1, allowing centralspindlin to function as a regulator of spindle midzone formation and as an activator of RhoA at the equatorial cortex.
MeSH term(s)	Animals ; Aurora Kinase B/genetics ; Aurora Kinase B/metabolism ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Cytokinesis ; Enzyme Activation ; HeLa Cells ; Humans ; Microtubule-Associated Proteins/genetics ; Microtubule-Associated Proteins/metabolism ; Microtubules/enzymology ; Microtubules/genetics ; Phosphoproteins/genetics ; Phosphoproteins/metabolism ; Protein Serine-Threonine Kinases/genetics ; Protein Serine-Threonine Kinases/metabolism ; Protein Transport ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins/metabolism ; Signal Transduction ; Spindle Apparatus/enzymology ; Spindle Apparatus/genetics ; rhoA GTP-Binding Protein/genetics ; rhoA GTP-Binding Protein/metabolism ; Polo-Like Kinase 1
Chemical Substances	CYK-4 protein, C elegans ; Caenorhabditis elegans Proteins ; Cell Cycle Proteins ; Microtubule-Associated Proteins ; PRC1 protein, human ; Phosphoproteins ; Proto-Oncogene Proteins ; SPD-1 protein, C elegans ; spindlin ; RHOA protein, human (124671-05-2) ; AURKB protein, human (EC 2.7.11.1) ; Aurora Kinase B (EC 2.7.11.1) ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; rhoA GTP-Binding Protein (EC 3.6.5.2)
Language	English
Publishing date	2019-02-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	218154-x
ISSN	1540-8140 ; 0021-9525
ISSN (online)	1540-8140
ISSN	0021-9525
DOI	10.1083/jcb.201805036
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Article ; Online: Untangling the contribution of Haspin and Bub1 to Aurora B function during mitosis.

Hadders, Michael A / Hindriksen, Sanne / Truong, My Anh / Mhaskar, Aditya N / Wopken, J Pepijn / Vromans, Martijn J M / Lens, Susanne M A

The Journal of cell biology

2020 Volume 219, Issue 3

Abstract: Aurora B kinase is essential for faithful chromosome segregation during mitosis. During (pro)metaphase, Aurora B is concentrated at the inner centromere by the kinases Haspin and Bub1. However, how Haspin and Bub1 collaborate to control Aurora B activity ...

Abstract	Aurora B kinase is essential for faithful chromosome segregation during mitosis. During (pro)metaphase, Aurora B is concentrated at the inner centromere by the kinases Haspin and Bub1. However, how Haspin and Bub1 collaborate to control Aurora B activity at centromeres remains unclear. Here, we show that either Haspin or Bub1 activity is sufficient to recruit Aurora B to a distinct chromosomal locus. Moreover, we identified a small, Bub1 kinase-dependent Aurora B pool that supported faithful chromosome segregation in otherwise unchallenged cells. Joined inhibition of Haspin and Bub1 activities fully abolished Aurora B accumulation at centromeres. While this impaired the correction of erroneous KT-MT attachments, it did not compromise the mitotic checkpoint, nor the phosphorylation of the Aurora B kinetochore substrates Hec1, Dsn1, and Knl1. This suggests that Aurora B substrates at the kinetochore are not phosphorylated by centromere-localized pools of Aurora B, and calls for a reevaluation of the current spatial models for how tension affects Aurora B-dependent kinetochore phosphorylation.
MeSH term(s)	Aurora Kinase B/genetics ; Aurora Kinase B/metabolism ; Chromosomal Proteins, Non-Histone/genetics ; Chromosomal Proteins, Non-Histone/metabolism ; Chromosome Segregation ; Cytoskeletal Proteins/genetics ; Cytoskeletal Proteins/metabolism ; HCT116 Cells ; Humans ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Kinesins/genetics ; Kinesins/metabolism ; Kinetochores/enzymology ; M Phase Cell Cycle Checkpoints ; Microtubule-Associated Proteins/genetics ; Microtubule-Associated Proteins/metabolism ; Microtubules/enzymology ; Microtubules/genetics ; Mitosis ; Phosphorylation ; Protein Serine-Threonine Kinases/genetics ; Protein Serine-Threonine Kinases/metabolism ; Signal Transduction ; Time Factors
Chemical Substances	Chromosomal Proteins, Non-Histone ; Cytoskeletal Proteins ; DSN1 protein, human ; Intracellular Signaling Peptides and Proteins ; KIF2C protein, human ; Knl1 protein, human ; Microtubule-Associated Proteins ; NDC80 protein, human ; AURKB protein, human (EC 2.7.11.1) ; Aurora Kinase B (EC 2.7.11.1) ; BUB1 protein, human (EC 2.7.11.1) ; HASPIN protein, human (EC 2.7.11.1) ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; Kinesins (EC 3.6.4.4)
Language	English
Publishing date	2020-02-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218154-x
ISSN	1540-8140 ; 0021-9525
ISSN (online)	1540-8140
ISSN	0021-9525
DOI	10.1083/jcb.201907087
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Article ; Online: Functionality of the chromosomal passenger complex in cancer.

Hindriksen, Sanne / Meppelink, Amanda / Lens, Susanne M A

Biochemical Society transactions

2015 Volume 43, Issue 1, Page(s) 23–32

Abstract: The evolutionary conserved chromosomal passenger complex (CPC) is essential for faithful transmission of the genome during cell division. Perturbation of this complex in cultured cells gives rise to chromosome segregation errors and cytokinesis failure ... ...

Abstract	The evolutionary conserved chromosomal passenger complex (CPC) is essential for faithful transmission of the genome during cell division. Perturbation of this complex in cultured cells gives rise to chromosome segregation errors and cytokinesis failure and as a consequence the ploidy status of the next generation of cells is changed. Aneuploidy and chromosomal instability (CIN) is observed in many human cancers, but whether this may be caused by deregulation of the CPC is unknown. In the present review, we discuss if and how a dysfunctional CPC could contribute to CIN in cancer.
MeSH term(s)	Animals ; Aurora Kinase B/metabolism ; Cell Cycle Proteins/metabolism ; Chromosomal Instability ; Chromosomal Proteins, Non-Histone/metabolism ; Chromosome Segregation ; Cytokinesis ; Humans ; Inhibitor of Apoptosis Proteins/metabolism ; Multiprotein Complexes/physiology ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology
Chemical Substances	BIRC5 protein, human ; CDCA8 protein, human ; Cell Cycle Proteins ; Chromosomal Proteins, Non-Histone ; INCENP protein, human ; Inhibitor of Apoptosis Proteins ; Multiprotein Complexes ; AURKB protein, human (EC 2.7.11.1) ; Aurora Kinase B (EC 2.7.11.1)
Language	English
Publishing date	2015-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	184237-7
ISSN	1470-8752 ; 0300-5127
ISSN (online)	1470-8752
ISSN	0300-5127
DOI	10.1042/BST20140275
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