Project information
Vnitřní vlastnosti RAD51 vlákna a jeho biologické regulace
- Project Identification
- GA17-17720S
- Project Period
- 1/2017 - 12/2019
- Investor / Pogramme / Project type
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Czech Science Foundation
- Standard Projects
- MU Faculty or unit
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Faculty of Medicine
- doc. Mgr. Lumír Krejčí, Ph.D.
- Mgr. Veronika Altmannová, Ph.D.
- Bc. Ondrej Beláň
- Mgr. Lenka Hejmalová
- RNDr. Mário Špírek, PhD.
Homologous recombination is an essential mechanism for the repair of DNA double-strand breaks and damaged replication forks. HR is initiated by the formation of a RAD51 helical nucleoprotein filament on single stranded DNA, which is able to search for and invade homologous duplex DNA to form a joint molecule. Although, RAD51 is unable to work alone and is reliant on co-factors (BRCA2 and RAD51 paralogs,) to drive the HR reaction to completion a mechanistic understanding of how this is achieved is unclear. This proposal will bring together the unique expertise to investigate how the properties of the RAD51 nucleoprotein filament are modulated by HR co-factors. Through the integration of real-time kinetic measurements, microscale thermophoresis, single molecule and structural visualization studies, conformational dynamics, and validation in biological systems we will provide unprecedented insight into the mechanisms by which HR co-factors impact on the HR reaction and its relevance to development of cancer.
Publications
Total number of publications: 14
2018
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SAMHD1 acts at stalled replication forks to prevent interferon induction
Nature, year: 2018, volume: 557, edition: 7703, DOI
2017
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Fanconi-Anemia-Associated Mutations Destabilize RAD51 Filaments and Impair Replication Fork Protection
Cell Reports, year: 2017, volume: 21, edition: 2, DOI
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RECQ5 Helicase Cooperates with MUS81 Endonuclease in Processing Stalled Replication Forks at Common Fragile Sites during Mitosis
Molecular Cell, year: 2017, volume: 66, edition: 5, DOI
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Smarcal1-Mediated Fork Reversal Triggers Mre11-Dependent Degradation of Nascent DNA in the Absence of Brca2 and Stable Rad51 Nucleofilaments
Molecular Cell, year: 2017, volume: 67, edition: 5, DOI