Informace o projektu
Identification and characterization of proteins involved in metabolism of G-quadruplexes and R-loops and molecular mechanisms of their relationship with replication
- Kód projektu
- 21-22593X
- Období řešení
- 1/2021 - 12/2025
- Investor / Programový rámec / typ projektu
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Grantová agentura ČR
- EXPRO
- Fakulta / Pracoviště MU
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Lékařská fakulta
- doc. Mgr. Lumír Krejčí, Ph.D.
- Masaki Akita, PhD
- Mgr. Jakub Cibulka, PhD.
- Anna Černá
- Jana Gašpariková
- Mgr. María Victoria Marini Palomeque, Ph.D.
- Bc. Volha Maroz
- Fedor Nikulenkov, Ph.D.
- RNDr. Jana Procházková, Ph.D.
- Pounami Samadder, Ph.D.
- RNDr. Mário Špírek, PhD.
- Mgr. Magdaléna Zacpalová
- Spolupracující organizace
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Ústav molekulární genetiky AV ČR, v. v. i.
- Odpovědná osoba Mgr. Jana Dobrovolná, Ph.D.
DNA replication is an essential and one of the most complex processes in the cell. Not only exogenous DNA damage but also intrinsic DNA structures including G-quadruplexes (G4) and R-loops, their stabilization or unscheduled formation represent major replication obstacles with possible detrimental effects on genome integrity. Not surprisingly, those processes are pharmacologically targeted in anticancer therapy, despite the fact that only little is known about the underlying molecular mechanisms. It becomes apparent that maintenance of processive DNA replication requires sophisticated protein networks beyond the core replisome. Whether there is a direct crosstalk between G4 and R-loops, what proteins are involved in their homeostasis and what are the factors diversifying between their beneficial and pathological roles, is not well understood. The goals of our research are to identify proteins associated with G4 and R-loop structures and understand their roles in G4/R-loop formation and resolution as well as relationship to replication fork progression and associated repair.
Cíle udržitelného rozvoje
Masarykova univerzita se hlásí k cílům udržitelného rozvoje OSN, jejichž záměrem je do roku 2030 zlepšit podmínky a kvalitu života na naší planetě.
Publikace
Počet publikací: 9
2024
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Concurrent D-loop cleavage by Mus81 and Yen1 yields half-crossover precursors
Nucleic Acids Research, rok: 2024, DOI
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Mechanism of BCDX2-mediated RAD51 nucleation on short ssDNA stretches and fork DNA
Nucleic acids research, rok: 2024, DOI
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MutSβ-MutLβ-FANCJ axis mediates the restart of DNA replication after fork stalling at cotranscriptional G4/R-loops
Science advances, rok: 2024, ročník: 10, vydání: 6, DOI
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Physical interaction with Spo11 mediates the localisation of Mre11 to chromatin in meiosis and promotes its nuclease activity
Nucleic acids research, rok: 2024, ročník: 52, vydání: 8, DOI
2023
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MUS81 cleaves TOP1‑derived lesions and other DNA-protein cross‑links
BMC Biology, rok: 2023, ročník: 21, vydání: 1, DOI
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Recognition and coacervation of G-quadruplexes by a multifunctional disordered region in RECQ4 helicase
Nature Communications, rok: 2023, ročník: 14, vydání: 1, DOI
2022
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The role of bivalent ions in the regulation of D-loop extension mediated by DMC1 during meiotic recombination
iSCIENCE, rok: 2022, ročník: 25, vydání: 11, DOI
2021
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Nucleotide proofreading functions by nematode RAD51 paralogs facilitate optimal RAD51 filament function
Nature Communications, rok: 2021, ročník: 12, vydání: 1, DOI
2020
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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