Objective
The mechanisms that safeguard cells against aneuploidy are of great interest as aneuploidy contributes to tumorigenesis. To gain insight into these mechanisms, I studied the behavior of cells entering mitosis with damaged chromosomes. I used the endonuclease I-CreI to generate acentric chromosomes in Drosophila larvae. While I-CreI expression produces acentric chromosomes in the majority of dividing cells, remarkably, it has no effect on adult survival. Live studies reveal that acentric chromatids segregate efficiently to opposite poles. The acentric chromatid poleward movement is mediated through DNA tethers that connect the acentric fragment to its centric partner. Three highly conserved kinases, BubR1, Aurora B and Polo localize on the tether and facilitates the accurate segregation of acentric chromatids by maintaining the integrity of the tether.
Chromosome segregation must be tightly coordinated with cell division to ensure that cells do not divide before the chromosomes have cleared the cleavage plane. However, the mechanism that permits this coordination is unknown. To identify this mechanism, I studied the behavior of cells going through mitosis with abnormally long chromatids. I took advantage of my previous discovery that acentric chromosomes remain attached to their centric partners by a DNA tether. This tether effectively increases the size of sister chromatids during anaphase. Remarkably, the cell adapts to the size of the long chromatids by increasing in length. Cell elongation enables long chromatids to clear the cleavage plane in time for cell division to occur properly. This novel cell elongation mechanism involves myosin activity.
I have discovered two mechanisms that prevent aneuploidy: the tether-based acentric segregation and the elongation of the cell that clears chromatids from the cleavage plane. Since both are new processes, our understanding of the underlying mechanisms is limited. My proposal aims to decipher these mechanisms.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences genetics chromosomes
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
ERC-2012-StG_20111109
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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.
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.
Host institution
75794 PARIS
France
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.