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Chromosome self-clearing completes sister chromatid separation

Chromosome self-clearing completes sister chromatid separation

Objective

In this research program, we propose the new concept that sister chromatid separation in mitosis is completed as a result of the dynamic intrinsic structural changes of chromosomes, i.e. through cycles of regional chromosome stretching and recoiling, which we call the self-clearing mechanism of chromosomes. By developing several novel methods, we will establish this new concept and demonstrate that the self-clearing of chromosomes is an essential mechanism allowing complete removal of sister chromatid cohesion, and that it is a fundamentally conserved function from yeast to vertebrates. To maintain genetic integrity, eukaryotic cells must duplicate their chromosomes and subsequently segregate them to opposite poles of the cell, prior to cell division. Cohesion is established between sister chromatids during S phase and marks sister pairs to ensure proper chromosome segregation in the next mitosis. However, the cohesion must be eventually removed to allow sister chromatids to separate and segregate to opposite poles. Although recent studies have revealed how the removal of cohesion is initiated, it is still elusive how this removal is completed. Our project will address mechanisms promoting this process and will open up a new direction of research, regarding dynamic chromosome organization, in particular its compaction and condensation. At present, the structural basis for chromosome compaction and condensation is poorly understood. Our project will shed new light on this inscrutable scientific problem by revealing the process of chromosome self-clearing. The outcome of our research will give important clues to fundamental mechanisms for chromosome segregation and will contribute to our understanding of human diseases, such as cancer and congenital disorders, which are characterized by chromosome instability and aneuploidy.

Principal Investigator

Tomoyuki Tanaka (Prof.)

Host institution

UNIVERSITY OF DUNDEE

Address

Nethergate
Dd1 4hn Dundee

United Kingdom

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 2 304 081,60

Principal Investigator

Tomoyuki Tanaka (Prof.)

Administrative Contact

Diane Taylor (Ms.)

Beneficiaries (2)

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UNIVERSITY OF DUNDEE

United Kingdom

EU Contribution

€ 2 304 081,60

THE UNIVERSITY OF SUSSEX

United Kingdom

EU Contribution

€ 186 382,80

Project information

Grant agreement ID: 322682

Status

Closed project

  • Start date

    1 April 2013

  • End date

    30 September 2018

Funded under:

FP7-IDEAS-ERC

  • Overall budget:

    € 2 490 464,40

  • EU contribution

    € 2 490 464,40

Hosted by:

UNIVERSITY OF DUNDEE

United Kingdom