Explanipedia

Changes in the approach to the analysis and evaluation of inherited pathogenic TP53 variants Open

Barbora Konečná, Věra Krutílková, Petra Kleiblová, Libor Macůrek, Zdeněk Kleibl · 2025

The present work underscores a paradigm shift in the understanding of one of the most significant cancer predisposition syndromes and aims to stimulate further discussion on the organization of care for high-risk carriers of pathogenic TP5…

Case-Control Study for 23 Cancer Types With Functional Analysis of CHEK2 : Risk Estimation and Clinical Recommendations in East Asia Open

Yuri Takehara, Yoshiaki Usui, Lenka Stolařová, Petra Kleiblová, Yusuke Iwasaki , et al. · 2025

PURPOSE CHEK2 is the frequently detected cancer-predisposing gene in female breast cancer. In addition, the association with the risks of other cancer types has been suggested, and clinical management has also been discussed. Although clin…

In-frame germline TP53 variant impairs p53 oligomerization and predisposes to cancer Open

Lucie Vanikova, Eva Macháčková, Barbora Němcová, Jana Soukupová, Silvia Petrezsélyová , et al. · 2025

Germline loss-of-function variants in TP53 cause Li–Fraumeni syndrome (LFS) characterized by an early onset of various cancer types including sarcomas, adrenocortical carcinoma, and breast cancer. The most common are mutations in the DNA b…

An ATM-PPM1D Circuit Controls the Processing and Restart of DNA Replication Forks Open

Yiting Cao, Yingzheng Wang, Jumana Badar, Matous Palek, Khoula Jaber , et al. · 2025

In response to DNA replication stress, DNA damage signaling kinases inhibit origin firing and promote the remodeling and stabilization of replication forks, leading to a systemic reduction in DNA synthesis that protects genomic integrity. …

Protein structure and interactions elucidated with in-cell NMR for different cell cycle phases and in 3D human tissue models Open

Jan Ryneš, Eva Ištvánková, Michaela Krafčíková, Enrico Luchinat, Letizia Barbieri , et al. · 2025

Most of our knowledge of protein structure and function originates from experiments performed with purified proteins resuspended in dilute, buffered solutions. However, most proteins function in crowded intracellular environments with comp…

PPM1D activity promotes cellular transformation by preventing senescence and cell death Open

Miroslav Stoyanov, Andra S. Martinikova, Kateřina Matějková, Klára Horáčková, Petra Zemánková , et al. · 2024

Cell cycle checkpoints, oncogene-induced senescence and programmed cell death represent intrinsic barriers to tumorigenesis. Protein phosphatase magnesium-dependent 1 (PPM1D) is a negative regulator of the tumour suppressor p53 and has bee…

A comprehensive study evaluating germline FANCG variants in predisposition to breast and ovarian cancer Open

Jana Soukupová, Barbora Šťastná, Madiha Kanwal, J. Hojný, Petra Zemánková , et al. · 2024

Background Monoallelic germline pathogenic variants (GPVs) in five Fanconi anemia (FA) genes ( BRCA1/FANCS , BRCA2/FANCD1 , PALB2/FANCN , BRIP1/FANCJ , and RAD51C/FANCO ) confer an increased risk of breast (BC) and/or ovarian (OC) cancer, …

FAM110A promotes mitotic spindle formation by linking microtubules with actin cytoskeleton Open

Cecilia Aquino-Perez, Mahira Safaralizade, Roman Podhajecky, Hong Wang, Zdeněk Lánský , et al. · 2024

Precise segregation of chromosomes during mitosis requires assembly of a bipolar mitotic spindle followed by correct attachment of microtubules to the kinetochores. This highly spatiotemporally organized process is controlled by various mi…

eLife assessment: SOD1 is a synthetic-lethal target in PPM1D-mutant leukemia cells Open

Libor Macůrek · 2024

RAD18 directs DNA double-strand break repair by homologous recombination to post-replicative chromatin Open

Matous Palek, Natalie Palkova, Marta Černá, Klára Horáčková, Milena Hovhannisyan , et al. · 2024

RAD18 is an E3 ubiquitin ligase that prevents replication fork collapse by promoting DNA translesion synthesis and template switching. Besides this classical role, RAD18 has been implicated in homologous recombination; however, this functi…

eLife Assessment: SOD1 is a synthetic lethal target in PPM1D-mutant leukemia cells Open

Libor Macůrek · 2024

The DNA damage response is critical for maintaining genome integrity and is commonly disrupted in the development of cancer. PPM1D (protein phosphatase, Mg2+/Mn2+ dependent 1D) is a master negative regulator of the response; gain-of-functi…

Inducible protein expression in stably transfected cells paves the way toward in-cell NMR studies in defined physiological states and 3D tissue cultures. Open

Lukáš Trantı́rek, Silvie Foldynová-Trantírková, Jan Ryneš, Eva Ištvánková, Michaela Krafčíková , et al. · 2024

In-cell NMR spectroscopy is the sole technique for characterizing protein structure, dynamics, and interactions in living human cells at atomic resolution. However, its applications have been restricted to asynchronous single-cell suspensi…

Inducible protein expression in stably transfected cells paves the way toward in-cell NMR studies in defined physiological states and 3D tissue cultures. Open

Lukáš Trantı́rek, Silvie Foldynová-Trantírková, Jan Ryneš, Eva Ištvánková, Michaela Krafčíková , et al. · 2024

In-cell NMR spectroscopy is the sole technique for characterizing protein structure, dynamics, and interactions in living human cells at atomic resolution. However, its applications have been restricted to asynchronous single-cell suspensi…

Hematopoietic stem cell fate under the influence of Ser/Thr protein phosphatases Open

Meritxell Alberich-Jordà, Libor Macůrek · 2024

Not available.

Ppm1d truncating mutations promote the development of genotoxic stress-induced AML Open

Monika Burócziová, Petr Daněk, Anna Oravetzova, Zuzana Chalupová, Meritxell Alberich-Jordà , et al. · 2023

PPM1D activity promotes the replication stress caused by cyclin E1 overexpression Open

Andra S. Martinikova, Miroslav Stoyanov, Anna Oravetzova, Yannick P. Kok, Shibo Yu , et al. · 2023

Oncogene‐induced replication stress has been recognized as a major cause of genome instability in cancer cells. Increased expression of cyclin E1 caused by amplification of the CCNE1 gene is a common cause of replication stress in various …

Importance of Germline and Somatic Alterations in Human MRE11, RAD50, and NBN Genes Coding for MRN Complex Open

Barbora Otahalova, Z Volková, Jana Soukupová, Petra Kleiblová, Markéta Janatová , et al. · 2023

The MRE11, RAD50, and NBN genes encode for the nuclear MRN protein complex, which senses the DNA double strand breaks and initiates the DNA repair. The MRN complex also participates in the activation of ATM kinase, which coordinates DNA re…

Phosphorylation of TRF2 promotes its interaction with TIN2 and regulates DNA damage response at telomeres Open

Radka Storchova, Matous Palek, Natalie Palkova, Pavel Veverka, Tomáš Brom , et al. · 2023

Protein phosphatase magnesium-dependent 1 delta (PPM1D) terminates the cell cycle checkpoint by dephosphorylating the tumour suppressor protein p53. By targeting additional substrates at chromatin, PPM1D contributes to the control of DNA d…

Many Ways to the Cell Cycle Exit after Inhibition of CDK4/6 Open

Libor Macůrek · 2023

Cyclin-dependent kinases (CDKs) are master regulators of proliferation, and therefore they represent attractive targets for cancer therapy. Development of selective CDK4/6 inhibitors including palbociclib revolutionized the treatment of a…

CDC25B is required for the metaphase I-metaphase II transition in mouse oocytes Open

Ivana Ferencova, Michaela Vaškovičová, Dávid Drutovič, Lucie Knoblochová, Libor Macůrek , et al. · 2022

Mammalian oocytes are arrested at meiotic prophase I. The dual-specificity phosphatase CDC25B is essential for cyclin-dependent kinase 1 (CDK1) activation that drives resumption of meiosis. CDC25B reverses the inhibitory effect of the prot…

C53 Interacting with UFM1-Protein Ligase 1 Regulates Microtubule Nucleation in Response to ER Stress Open

Anastasiya Klebanovych, Stanislav Vinopal, Eduarda Dráberová, Vladimíra Sládková, Tetyana Sulimenko , et al. · 2022

ER distribution depends on microtubules, and ER homeostasis disturbance activates the unfolded protein response resulting in ER remodeling. CDK5RAP3 (C53) implicated in various signaling pathways interacts with UFM1-protein ligase 1 (UFL1)…

CK1‐mediated phosphorylation of FAM110A promotes its interaction with mitotic spindle and controls chromosomal alignment Open

Cecilia Aquino Perez, Monika Burócziová, Gabriela Jeníková, Libor Macůrek · 2021

A novel assay for screening WIP1 phosphatase substrates in nuclear extracts Open

Radka Storchova, Kamila Burdová, Matous Palek, René H. Medema, Libor Macůrek · 2021

Upon exposure to genotoxic stress, cells activate DNA damage response (DDR) that coordinates DNA repair with a temporal arrest in the cell cycle progression. DDR is triggered by activation of ataxia telangiectasia mutated/ataxia telangiect…

Author response for "A novel assay for screening WIP1 phosphatase substrates in nuclear extracts" Open

Radka Storchova, Kamila Burdová, Matous Palek, René H. Medema, Libor Macůrek · 2021

Cyclin A2 localises in the cytoplasm at the S/G2 transition to activate PLK1 Open

Helena Silva Cascales, Kamila Burdová, Anna Middleton, Vladislav Kuzin, Erik Müllers , et al. · 2021

Cyclin A2 is a key regulator of the cell cycle, implicated both in DNA replication and mitotic entry. Cyclin A2 participates in feedback loops that activate mitotic kinases in G2 phase, but why active Cyclin A2-CDK2 during the S phase does…

C53 interacting with UFM1-protein ligase 1 regulates microtubule nucleation in response to ER stress Open

Anastasiya Klebanovych, Stanislav Vinopal, Eduarda Dráberová, Vladimíra Sládková, Tetyana Sulimenko , et al. · 2020

ER distribution depends on microtubules, and ER homeostasis disturbance activates the unfolded protein response resulting in ER remodeling. CDK5RAP3 (C53) implicated in various signaling pathways interacts with UFM1-protein ligase 1 (UFL1)…

CHEK2 Germline Variants in Cancer Predisposition: Stalemate Rather than Checkmate Open

Lenka Stolařová, Petra Kleiblová, Markéta Janatová, Jana Soukupová, Petra Zemánková , et al. · 2020

Germline alterations in many genes coding for proteins regulating DNA repair and DNA damage response (DDR) to DNA double-strand breaks (DDSB) have been recognized as pathogenic factors in hereditary cancer predisposition. The ATM-CHEK2-p53…

Identification of Germline Mutations in Melanoma Patients with Early Onset, Double Primary Tumors, or Family Cancer History by NGS Analysis of 217 Genes Open

Lenka Stolařová, Sandra Jelínková, Radka Storchova, Eva Macháčková, Petra Zemánková , et al. · 2020

Cutaneous melanoma is the deadliest skin malignity with a rising prevalence worldwide. Patients carrying germline mutations in melanoma-susceptibility genes face an increased risk of melanoma and other cancers. To assess the spectrum of ge…

Truncated PPM1D Prevents Apoptosis in the Murine Thymus and Promotes Ionizing Radiation-Induced Lymphoma Open

Andra S. Martinikova, Monika Burócziová, Miroslav Stoyanov, Libor Macůrek · 2020

Genome integrity is protected by the cell-cycle checkpoints that prevent cell proliferation in the presence of DNA damage and allow time for DNA repair. The transient checkpoint arrest together with cellular senescence represent an intrins…

Phosphorylation of PLK3 Is Controlled by Protein Phosphatase 6 Open

Cecilia Aquino Perez, Matous Palek, Lenka Stolařová, Patrick von Morgen, Libor Macůrek · 2020

Polo-like kinases play essential roles in cell cycle control and mitosis. In contrast to other members of this kinase family, PLK3 has been reported to be activated upon cellular stress including DNA damage, hypoxia and osmotic stress. Her…

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