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Content archived on 2024-05-29

Elucidation of the mechanism of sister Chromatid Cohesion

Objective

Cell division is a fundamental process in the growth and proliferation of all living organisms. This entails the accurate duplication and the faithful distribution of the genome from the mother cell to the daughter cells.

For this purpose, the ring-like cohesin complex physically links sister chromatids to prevent their premature separation during cell division. However, despite its importance in chromosomal stability, little is known about the interaction of cohesin with chromosomes.

Previous laboratory findings have revealed that cohesin relocates from its initial binding sites and accumulates at sites of convergent transcriptional termination along S. cerevisiae chromosomes. Moreover, while the underlying DNA sequence does not determine the placement of cohesin, changes in the transcriptional status affect cohesin localization, with transcriptional induction of a silent gene resulting in downstream repositioning of cohesin.

To elucidate the nature of cohesin binding to chromosomes, this project will investigate the mechanism of cohesin relocation in vivo. Specifically, this study will
- characterize the translocation of cohesin upon induction of transcription and
- assess the behaviour of cohesin during centromere breathing.

This analysis will test whether cohesin relocation occurs by sliding along chromosomes or by reloading of the complex downstream of the initial binding site. To this end, chromatin immunoprecipitation followed by hybridization to a high-density gene chip microarray will be employed.

Since cohesin is essential for mediating chromosome stability during cell division, these findings will provide novel insights about the maintenance of genomic integrity and will have significant implications for diseases caused by chromosomal instabilities, including congenital birth defects and cancer.

Fields of science (EuroSciVoc)

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Keywords

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Topic(s)

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Call for proposal

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FP6-2005-MOBILITY-7
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Funding Scheme

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IIF - Marie Curie actions-Incoming International Fellowships

Coordinator

CANCER RESEARCH UK LONDON RESEARCH INSTITUTE
EU contribution
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Total cost

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