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View article: Discovery of two structurally distinct classes of inhibitors targeting the nuclease MUS81 and enhancing efficacy of chemotherapy in cancer cells
Discovery of two structurally distinct classes of inhibitors targeting the nuclease MUS81 and enhancing efficacy of chemotherapy in cancer cells Open
Nucleases are emerging as promising pharmacological targets due to their essential role in maintaining genomic stability, which is crucial for cellular viability and can be exploited in the prevention and treatment of various diseases, inc…
View article: Dbl2 interacts with helicases and an endonuclease to maintain the integrity of repetitive regions
Dbl2 interacts with helicases and an endonuclease to maintain the integrity of repetitive regions Open
Helicases and endonucleases play crucial roles in genome maintenance by unwinding or cleaving various forms of DNA and RNA structures in order to facilitate essential biological processes, such as DNA replication and recombination. Here, w…
View article: RECQ4-MUS81 interaction contributes to telomere maintenance with implications to Rothmund-Thomson syndrome
RECQ4-MUS81 interaction contributes to telomere maintenance with implications to Rothmund-Thomson syndrome Open
Replication stress, particularly in hard-to-replicate regions such as telomeres and centromeres, leads to the accumulation of replication intermediates that must be processed to ensure proper chromosome segregation. In this study, we ident…
View article: Withdrawal: Cooperativity of Mus81·Mms4 with Rad54 in the resolution of recombination and replication intermediates
Withdrawal: Cooperativity of Mus81·Mms4 with Rad54 in the resolution of recombination and replication intermediates Open
View article: Mechanism of BCDX2-mediated RAD51 nucleation on short ssDNA stretches and fork DNA
Mechanism of BCDX2-mediated RAD51 nucleation on short ssDNA stretches and fork DNA Open
Homologous recombination (HR) factors are crucial for DSB repair and processing stalled replication forks. RAD51 paralogs, including RAD51B, RAD51C, RAD51D, XRCC2 and XRCC3, have emerged as essential tumour suppressors, forming two subcomp…
View article: Concurrent D-loop cleavage by Mus81 and Yen1 yields half-crossover precursors
Concurrent D-loop cleavage by Mus81 and Yen1 yields half-crossover precursors Open
Homologous recombination involves the formation of branched DNA molecules that may interfere with chromosome segregation. To resolve these persistent joint molecules, cells rely on the activation of structure-selective endonucleases (SSEs)…
View article: RAD51 separation of function mutation disables replication fork maintenance but preserves DSB repair
RAD51 separation of function mutation disables replication fork maintenance but preserves DSB repair Open
Homologous recombination (HR) protects replication forks (RFs) and repairs DNA double-strand breaks (DSBs). Within HR, BRCA2 regulates RAD51 via two interaction regions: the BRC repeats to form filaments on single-stranded DNA and exon 27 …
View article: Physical interaction with Spo11 mediates the localisation of Mre11 to chromatin in meiosis and promotes its nuclease activity
Physical interaction with Spo11 mediates the localisation of Mre11 to chromatin in meiosis and promotes its nuclease activity Open
Meiotic recombination is of central importance for the proper segregation of homologous chromosomes, but also for creating genetic diversity. It is initiated by the formation of double-strand breaks (DSBs) in DNA catalysed by evolutionaril…
View article: MutSβ-MutLβ-FANCJ axis mediates the restart of DNA replication after fork stalling at cotranscriptional G4/R-loops
MutSβ-MutLβ-FANCJ axis mediates the restart of DNA replication after fork stalling at cotranscriptional G4/R-loops Open
Transcription-replication conflicts (TRCs) induce formation of cotranscriptional RNA:DNA hybrids (R-loops) stabilized by G-quadruplexes (G4s) on the displaced DNA strand, which can cause fork stalling. Although it is known that these stall…
View article: Discovery of New Inhibitors of Nuclease Mre11
Discovery of New Inhibitors of Nuclease Mre11 Open
View article: RECQ4-MUS81 interaction safeguards hard-to-replicate regions to prevent genome instability and Rothmund-Thomson syndrome
RECQ4-MUS81 interaction safeguards hard-to-replicate regions to prevent genome instability and Rothmund-Thomson syndrome Open
Replication stress, resulting from hard-to-replicate regions, leads to the accumulation of replication intermediates that need to be processed to ensure successful chromosome segregation. Here we show that RECQ4 physically interacts with M…
View article: Recognition and coacervation of G-quadruplexes by a multifunctional disordered region in RECQ4 helicase
Recognition and coacervation of G-quadruplexes by a multifunctional disordered region in RECQ4 helicase Open
View article: Concurrent D-loop cleavage by Mus81 and Yen1 yields half-crossover precursors
Concurrent D-loop cleavage by Mus81 and Yen1 yields half-crossover precursors Open
Homologous recombination involves the formation of branched DNA molecules that may interfere with chromosome segregation. To resolve these persistent joint molecules, cells rely on the activation of structure-selective endonucleases (SSEs)…
View article: MUS81 cleaves TOP1-derived lesions and other DNA–protein cross-links
MUS81 cleaves TOP1-derived lesions and other DNA–protein cross-links Open
View article: Supplementary Methods from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation
Supplementary Methods from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation Open
Detail description of Material and Methods
View article: Supplementary Methods from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation
Supplementary Methods from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation Open
Detail description of Material and Methods
View article: Data from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation
Data from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation Open
Checkpoint-mediated dependency of tumor cells can be deployed to selectively kill them without substantial toxicity to normal cells. Specifically, loss of CHK1, a serine threonine kinase involved in the surveillance of the G2–M …
View article: Data from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation
Data from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation Open
Checkpoint-mediated dependency of tumor cells can be deployed to selectively kill them without substantial toxicity to normal cells. Specifically, loss of CHK1, a serine threonine kinase involved in the surveillance of the G2–M …
View article: Supplemetary Tables from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation
Supplemetary Tables from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation Open
Table S1. Mouse plasma protein binding profile of MU380 and SCH900776. Table S2. IC50 determination of main P450 cytochrome isoforms in human liver microsomes. Table S3. A) Evaluation of MU380 and SCH900776 disappearance with time in the p…
View article: Supplementary file-Synthesis from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation
Supplementary file-Synthesis from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation Open
Detail description of synthesis and supporting data
View article: Supplementary Legends from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation
Supplementary Legends from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation Open
Supplementary Legends for Supplemetary Figure S1 - S11
View article: Supplemetary Tables from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation
Supplemetary Tables from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation Open
Table S1. Mouse plasma protein binding profile of MU380 and SCH900776. Table S2. IC50 determination of main P450 cytochrome isoforms in human liver microsomes. Table S3. A) Evaluation of MU380 and SCH900776 disappearance with time in the p…
View article: Supplementary Figures from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation
Supplementary Figures from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation Open
Figure S1. In vitro profiling of SCH900776 and its selected analogs. Figure S2. Analogs of MU380 with the N-trifluoromethylpyrazol pharmacophore. Figure S3. Dot plots of flow cytometric analysis using γH2AX and Annexin V staining related …
View article: Supplementary Figures from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation
Supplementary Figures from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation Open
Figure S1. In vitro profiling of SCH900776 and its selected analogs. Figure S2. Analogs of MU380 with the N-trifluoromethylpyrazol pharmacophore. Figure S3. Dot plots of flow cytometric analysis using γH2AX and Annexin V staining related …
View article: Supplementary Legends from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation
Supplementary Legends from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation Open
Supplementary Legends for Supplemetary Figure S1 - S11
View article: Supplementary file-Synthesis from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation
Supplementary file-Synthesis from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation Open
Detail description of synthesis and supporting data
View article: Additional file 10 of MUS81 cleaves TOP1-derived lesions and other DNA–protein cross-links
Additional file 10 of MUS81 cleaves TOP1-derived lesions and other DNA–protein cross-links Open
Additional file 10. Individual data values. Individual data values used for the graphs present in this paper.
View article: The role of bivalent ions in the regulation of D-loop extension mediated by DMC1 during meiotic recombination
The role of bivalent ions in the regulation of D-loop extension mediated by DMC1 during meiotic recombination Open
View article: Nucleotide proofreading functions by nematode RAD51 paralogs facilitate optimal RAD51 filament function
Nucleotide proofreading functions by nematode RAD51 paralogs facilitate optimal RAD51 filament function Open
View article: Single-molecule visualization of human RECQ5 interactions with single-stranded DNA recombination intermediates
Single-molecule visualization of human RECQ5 interactions with single-stranded DNA recombination intermediates Open
RECQ5 is one of five RecQ helicases found in humans and is thought to participate in homologous DNA recombination by acting as a negative regulator of the recombinase protein RAD51. Here, we use kinetic and single molecule imaging methods …