Informace o projektu
Vnitřní vlastnosti RAD51 vlákna a jeho biologické regulace
- Kód projektu
- GA17-17720S
- Období řešení
- 1/2017 - 12/2019
- Investor / Programový rámec / typ projektu
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Grantová agentura ČR
- Standardní projekty
- Fakulta / Pracoviště MU
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Lékařská fakulta
- 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.
Publikace
Počet publikací: 14
2021
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In Vitro Characterization of Sumoylation of HR Proteins
Homologous Recombination: Methods and Protocols, rok: 2021, počet stran: 20 s.
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Single-molecule visualization of human RECQ5 interactions with single-stranded DNA recombination intermediates
Nucleic acids research, rok: 2021, ročník: 49, vydání: 1, DOI
2020
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DSS1 interacts with and stimulates RAD52 to promote the repair of DSBs
Nucleic Acids Research, rok: 2020, ročník: 48, vydání: 2, DOI
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RAD51-dependent recruitment of TERRA lncRNA to telomeres through R-loops
Nature, rok: 2020, ročník: 587, vydání: 7833, DOI
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SAMHD1 acts at stalled replication forks to prevent interferon induction
Comptes Rendus - Biologies, rok: 2020, ročník: 343, vydání: 1, DOI
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TREX2 Exonuclease Causes Spontaneous Mutations and Stress-Induced Replication Fork Defects in Cells Expressing RAD51(K133A)
Cell Reports, rok: 2020, ročník: 33, vydání: 12, DOI
2019
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CDK12 controls G1/S progression by regulating RNAPII processivity at core DNA replication genes
EMBO reports, rok: 2019, ročník: 20, vydání: 9, DOI
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Deficiency and haploinsufficiency of histone macroH2A1.1 in mice recapitulate hematopoietic defects of human myelodysplastic syndrome
CLINICAL EPIGENETICS, rok: 2019, ročník: 11, vydání: 1, DOI
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Sumoylation regulates the stability and nuclease activity of Saccharomyces cerevisiae Dna2
COMMUNICATIONS BIOLOGY, rok: 2019, ročník: 2, vydání: MAY 8 2019, DOI
2018
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Human RAD51 rapidly forms intrinsically dynamic nucleoprotein filaments modulated by nucleotide binding state
Nucleic Acids Research, rok: 2018, ročník: 46, vydání: 8, DOI