Mitotic regulation by Polo-like kinase 1 and the chromosomal passenger complex

Dissertation

Leena Ahonen

Research output: ThesisDissertationCollection of Articles

Abstract

During mitosis, the duplicated genome must be accurately divided between two daughter cells. Polo-like kinase 1 (Plk1) and Aurora B kinase, together with its binding partners Incenp, Survivin and Borealin (chromosomal passenger complex, CPC), have key roles in coordinating mitotic events. The accuracy of cell division is safeguarded by a signaling cascade termed the mitotic spindle checkpoint (SC), which ensures that chromosomes are not physically separated before correct bipolar attachments have been formed between kinetochores and spindle microtubules (MT). An inhibitory "wait anaphase" signal, which delays chromosome separation (anaphase onset), is created at individual kinetochores and broadcasted throughout the cell in response to lack of kinetochore-microtubule (kMT) attachment or proper interkinetochore tension. It is believed that the fast turnover of SC molecules at kinetochores contributes to the cell's ability to produce this signal and enables rapid responses to changing cellular conditions. Kinetochores that lack MT attachment and tension express a certain phosphoepitope called the 3F3/2 phosphoepitope, which has been linked to SC signaling. In the experimental part, we investigated the regulation of the 3F3/2 phosphoepitope, analyzed whether CPC molecules turn over at centromeres, and dissected the mitotic roles of the CPC using a microinjection technique that allowed precise temporal control over its function. We found that the kinetochore 3F3/2 phosphoepitope is created by Plk1, and that CPC proteins exhibit constant exchange at centromeres. Moreover, we found that CPC function is necessary in the regulation of chromatid movements and spindle morphology in anaphase. In summary, we identified new functions of key mitotic regulators Plk1 and CPC, and provided insighs into the coordination of mitotic events.
Original languageEnglish
QualificationDoctor Degree
Awarding Institution
  • University of Turku
Supervisors/Advisors
  • Kallio, Marko, Supervisor, External person
Place of PublicationTurku
Publisher
Print ISBNs978-951-29-3734-9
Electronic ISBNs978-951-29-3735-6
Publication statusPublished - 2008
MoE publication typeG5 Doctoral dissertation (article)

Fingerprint

Kinetochores
Anaphase
Microtubules
Centromere
Aurora Kinase B
Chromosomes
M Phase Cell Cycle Checkpoints
Chromatids
Microinjections
Mitosis
Cell Division
polo-like kinase 1
Genome
Proteins

Keywords

  • Mitosis
  • SC
  • Plk1
  • Aurora B
  • CPC
  • 3F3/2 Phosphoepitope
  • Kinetochore
  • mitoosi
  • mitoottinen tarkastuspiste
  • 3F3/2-fosforpitooppi
  • kinetokori

Cite this

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title = "Mitotic regulation by Polo-like kinase 1 and the chromosomal passenger complex: Dissertation",
abstract = "During mitosis, the duplicated genome must be accurately divided between two daughter cells. Polo-like kinase 1 (Plk1) and Aurora B kinase, together with its binding partners Incenp, Survivin and Borealin (chromosomal passenger complex, CPC), have key roles in coordinating mitotic events. The accuracy of cell division is safeguarded by a signaling cascade termed the mitotic spindle checkpoint (SC), which ensures that chromosomes are not physically separated before correct bipolar attachments have been formed between kinetochores and spindle microtubules (MT). An inhibitory {"}wait anaphase{"} signal, which delays chromosome separation (anaphase onset), is created at individual kinetochores and broadcasted throughout the cell in response to lack of kinetochore-microtubule (kMT) attachment or proper interkinetochore tension. It is believed that the fast turnover of SC molecules at kinetochores contributes to the cell's ability to produce this signal and enables rapid responses to changing cellular conditions. Kinetochores that lack MT attachment and tension express a certain phosphoepitope called the 3F3/2 phosphoepitope, which has been linked to SC signaling. In the experimental part, we investigated the regulation of the 3F3/2 phosphoepitope, analyzed whether CPC molecules turn over at centromeres, and dissected the mitotic roles of the CPC using a microinjection technique that allowed precise temporal control over its function. We found that the kinetochore 3F3/2 phosphoepitope is created by Plk1, and that CPC proteins exhibit constant exchange at centromeres. Moreover, we found that CPC function is necessary in the regulation of chromatid movements and spindle morphology in anaphase. In summary, we identified new functions of key mitotic regulators Plk1 and CPC, and provided insighs into the coordination of mitotic events.",
keywords = "Mitosis, SC, Plk1, Aurora B, CPC, 3F3/2 Phosphoepitope, Kinetochore, mitoosi, mitoottinen tarkastuspiste, 3F3/2-fosforpitooppi, kinetokori",
author = "Leena Ahonen",
note = "TK403",
year = "2008",
language = "English",
isbn = "978-951-29-3734-9",
series = "Annales Universitatis Turkuensis: D Medica - Odontologica",
publisher = "University of Turku",
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Ahonen, L 2008, 'Mitotic regulation by Polo-like kinase 1 and the chromosomal passenger complex: Dissertation', Doctor Degree, University of Turku, Turku.

Mitotic regulation by Polo-like kinase 1 and the chromosomal passenger complex : Dissertation. / Ahonen, Leena.

Turku : University of Turku, 2008. 74 p.

Research output: ThesisDissertationCollection of Articles

TY - THES

T1 - Mitotic regulation by Polo-like kinase 1 and the chromosomal passenger complex

T2 - Dissertation

AU - Ahonen, Leena

N1 - TK403

PY - 2008

Y1 - 2008

N2 - During mitosis, the duplicated genome must be accurately divided between two daughter cells. Polo-like kinase 1 (Plk1) and Aurora B kinase, together with its binding partners Incenp, Survivin and Borealin (chromosomal passenger complex, CPC), have key roles in coordinating mitotic events. The accuracy of cell division is safeguarded by a signaling cascade termed the mitotic spindle checkpoint (SC), which ensures that chromosomes are not physically separated before correct bipolar attachments have been formed between kinetochores and spindle microtubules (MT). An inhibitory "wait anaphase" signal, which delays chromosome separation (anaphase onset), is created at individual kinetochores and broadcasted throughout the cell in response to lack of kinetochore-microtubule (kMT) attachment or proper interkinetochore tension. It is believed that the fast turnover of SC molecules at kinetochores contributes to the cell's ability to produce this signal and enables rapid responses to changing cellular conditions. Kinetochores that lack MT attachment and tension express a certain phosphoepitope called the 3F3/2 phosphoepitope, which has been linked to SC signaling. In the experimental part, we investigated the regulation of the 3F3/2 phosphoepitope, analyzed whether CPC molecules turn over at centromeres, and dissected the mitotic roles of the CPC using a microinjection technique that allowed precise temporal control over its function. We found that the kinetochore 3F3/2 phosphoepitope is created by Plk1, and that CPC proteins exhibit constant exchange at centromeres. Moreover, we found that CPC function is necessary in the regulation of chromatid movements and spindle morphology in anaphase. In summary, we identified new functions of key mitotic regulators Plk1 and CPC, and provided insighs into the coordination of mitotic events.

AB - During mitosis, the duplicated genome must be accurately divided between two daughter cells. Polo-like kinase 1 (Plk1) and Aurora B kinase, together with its binding partners Incenp, Survivin and Borealin (chromosomal passenger complex, CPC), have key roles in coordinating mitotic events. The accuracy of cell division is safeguarded by a signaling cascade termed the mitotic spindle checkpoint (SC), which ensures that chromosomes are not physically separated before correct bipolar attachments have been formed between kinetochores and spindle microtubules (MT). An inhibitory "wait anaphase" signal, which delays chromosome separation (anaphase onset), is created at individual kinetochores and broadcasted throughout the cell in response to lack of kinetochore-microtubule (kMT) attachment or proper interkinetochore tension. It is believed that the fast turnover of SC molecules at kinetochores contributes to the cell's ability to produce this signal and enables rapid responses to changing cellular conditions. Kinetochores that lack MT attachment and tension express a certain phosphoepitope called the 3F3/2 phosphoepitope, which has been linked to SC signaling. In the experimental part, we investigated the regulation of the 3F3/2 phosphoepitope, analyzed whether CPC molecules turn over at centromeres, and dissected the mitotic roles of the CPC using a microinjection technique that allowed precise temporal control over its function. We found that the kinetochore 3F3/2 phosphoepitope is created by Plk1, and that CPC proteins exhibit constant exchange at centromeres. Moreover, we found that CPC function is necessary in the regulation of chromatid movements and spindle morphology in anaphase. In summary, we identified new functions of key mitotic regulators Plk1 and CPC, and provided insighs into the coordination of mitotic events.

KW - Mitosis

KW - SC

KW - Plk1

KW - Aurora B

KW - CPC

KW - 3F3/2 Phosphoepitope

KW - Kinetochore

KW - mitoosi

KW - mitoottinen tarkastuspiste

KW - 3F3/2-fosforpitooppi

KW - kinetokori

M3 - Dissertation

SN - 978-951-29-3734-9

T3 - Annales Universitatis Turkuensis: D Medica - Odontologica

PB - University of Turku

CY - Turku

ER -