Project description
Understanding DNA double-strand break formation in meiosis
Gametes in sexually reproducing organisms undergo meiosis, a type of cell division that reduces the number of chromosomes. Meiosis depends on the formation of DNA double-strand breaks (DSBs) to drive recombination, ensuring genetic diversity and balanced haploid gametes. In yeast, DSBs are catalysed by various proteins that form a complex through a process known as RMM condensation which organises intracellular compartments and regulates the timing, location and coordination of DSB formation. The ERC-funded MeioticCondensate project aims to delineate the molecular mechanisms governing RMM condensation. Insights gained will enhance our understanding of genetic inheritance and biomolecular condensation as a key principle in cellular organisation and function.
Objective
Meiosis universally relies on the formation of DNA double-strand breaks (DSB) to initiate a genome-wide recombination program that promotes genetic diversity and is required to produce chromosomally-balanced haploid gametes. DSB formation is catalyzed by Spo11, which in acts in conjunction with nine essential partners in yeast, including the RMM proteins. We previously found that RMM undergoes DNA-dependent condensation, and proposed that this organizes intracellular sub-compartments within which controlled DSB formation takes place. The RMM proteins connect DSB formation to chromosome structure, and are subject to overlapping regulatory pathways that control the timing, position, and number of DSBs. However, the molecular assemblies that catalyze DSB formation and the mechanisms whereby they are regulated remain poorly understood. Here, I propose an approach that takes advantage of our established biochemical and molecular genetics techniques, combined with the development of novel methodologies, to unravel the central role of RMM condensation in DSB formation. Specifically, we will address the following outstanding questions: (1) What are the mechanisms of post-translational control of RMM condensation? (2) How does transcription impact condensation and DSB formation? (3) How does the chromosome axis affect RMM condensation? (4) What are the quantitative molecular interactions that underlie condensation? (5) Which proteins associate with RMM condensates? (6) What is the impact of RMM condensation on chromatin structure? This proposal harnesses our current knowledge of the molecular properties of DSB proteins to explore new models and hypotheses regarding the relationships between the DSB machinery and the cell. My goal is to gain insights into the molecular processes that underlie genetic inheritance. In addition, this work will contribute to our understanding of the role of biomolecular condensation as an organizing principle of cellular structure and function.
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 biochemistry biomolecules proteins
- natural sciences biological sciences genetics heredity
- natural sciences biological sciences genetics chromosomes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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(opens in new window) ERC-2023-COG
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1348 LOUVAIN LA NEUVE
Belgium
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