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IMPACT OF DNA REPLICATION ON EPIGENETICS

Objective

During lineage propagation, cells must duplicate their genetic and epigenetic information to maintain cell identity. However, the mechanisms underlying the maintenance of epigenetic information in dividing cells remain largely unknown.

In S phase, progression of DNA replication forks provokes a genome-wide disruption of the epigenetic information. While nucleosomes are rapidly reassembled on newly replicated DNA, full restoration of epigenetic information is not completed until after mitosis. This proposal aims to reveal how cells restore epigenetic information after DNA replication. To address this question, I have developed a new technology called Nascent Chromatin Capture (NCC). NCC is a powerful and versatile method that allows purification and analysis over time of proteins associated with replicated DNA. (1) I will identify novel mechanisms in chromatin restoration in mother and daughter cells. To this end I will combine NCC with quantitative mass spectrometry, high-throughput microscopy and screening technologies. Furthermore, I will develop original strategies to directly study the impact of chromatin restoration defects on genome integrity and differentiation potential. (2) It remains unknown whether specific loci as DNA replication origins, have a particular mode of restoration. I propose to develop a new technology, NCC-Ori, to capture chromatin at DNA replication origins. This innovative cutting edge technology will permit to unravel molecular mechanisms that underpin chromatin restoration at these specific sites and uncover chromatin determinants of replication timing and origin activation. (3) Newly identified players that are linked to human diseases will be characterized in order to understand their role in disease etiology and their therapeutic potential.

Altogether, these integrated approaches should provide new insights into the molecular mechanisms that coordinate genome and epigenome maintenance across cell generations.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-STG - Starting Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2016-STG

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Host institution

UNIVERSITY OF DUNDEE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 444 081,00
Address
Nethergate
DD1 4HN Dundee
United Kingdom

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Region
Scotland Eastern Scotland Angus and Dundee City
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 444 081,00

Beneficiaries (1)

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