A5046067475- DNA Repair Mechanisms
- Cancer Genomics and Diagnostics
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- Epigenetics and DNA Methylation
- Mitochondrial Function and Pathology
- Viral-associated cancers and disorders
- Genomic variations and chromosomal abnormalities
- Health, Environment, Cognitive Aging
- interferon and immune responses
- Heat shock proteins research
- Genetic factors in colorectal cancer
- Enzyme Structure and Function
- Toxoplasma gondii Research Studies
- Cancer Research and Treatments
- DNA and Nucleic Acid Chemistry
- Immune Cell Function and Interaction
- Genomics and Chromatin Dynamics
- Chronic Lymphocytic Leukemia Research
- Telomeres, Telomerase, and Senescence
- Nuclear Structure and Function
- Genomics and Rare Diseases
- RNA modifications and cancer
Stevenage Bioscience Catalyst
2024
Memorial Sloan Kettering Cancer Center
2018-2022
Czech Academy of Sciences, Institute of Molecular Genetics
2015-2020
Czech Academy of Sciences
2015-2020
Institute of Molecular Genetics
2015
The APOBEC3 family of cytosine deaminases has been implicated in some the most prevalent mutational signatures cancer1-3. However, a causal link between endogenous enzymes and human cancer genomes not established, leaving mechanisms mutagenesis poorly understood. Here, to investigate mutagenesis, we deleted genes from cell lines that naturally generate APOBEC3-associated over time4. Analysis non-clustered clustered across whole-genome sequences 251 breast, bladder lymphoma line clones...
In response to genotoxic stress, cells protect their genome integrity by activation of a conserved DNA damage (DDR) pathway that coordinates repair and progression through the cell cycle. Extensive modification chromatin flanking lesion ATM kinase RNF8/RNF168 ubiquitin ligases enables recruitment various factors. Among them BRCA1 53BP1 are required for homologous recombination non-homologous end joining, respectively. Whereas mechanisms DDR relatively well understood in interphase cells,...
The MRN (MRE11–RAD50–NBS1) complex is essential for repair of DNA double-strand breaks and stalled replication forks. Mutations the subunit MRE11 cause hereditary cancer-susceptibility disease ataxia-telangiectasia-like disorder (ATLD). Here we show that directly interacts with PIH1D1, a heat-shock protein 90 cochaperone R2TP complex, which required assembly large complexes, such as RNA polymerase II, small nucleolar ribonucleoproteins mammalian target rapamycin 1. MRE11-PIH1D1 interaction...
Repair of damaged DNA is essential for maintaining genomic stability. TP53-binding protein 1 (53BP1) plays an important role in repair the double-strand breaks. Nuclear localisation 53BP1 depends on importin β and nucleoporin 153, but type location nuclear signal (NLS) have yet to be determined.Here, we show that import two basic regions, namely 1667-KRK-1669 1681-KRGRK-1685, which are both needed binding. Lysine 1667 interaction with its substitution arginine reduced 53BP1. Furthermore,...
Telomere crisis is linked with many of the genomic alterations found in cancer genomes. A new understanding how these arise points towards an active role for innate immune sensors during and to opportunities treatment diagnosis cancer.
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 be activated upon cellular stress including DNA damage, hypoxia osmotic stress. Here we knocked out human non-transformed RPE cells using CRISPR/Cas9-mediated gene editing. Surprisingly, find that loss does not impair stabilization HIF1α after hypoxia, phosphorylation the c-Jun dynamics damage response exposure ionizing radiation. Similarly,...
ABSTRACT The APOBEC3 family of cytidine deaminases is widely speculated to be a major source somatic mutations in cancer 1–3 . However, causal links between enzymes and human cells have not been established. identity the paralog(s) that may act as prime drivers mutagenesis mechanisms underlying different APOBEC3-associated mutational signatures are unknown. To directly investigate roles mutagenesis, candidate genes were deleted from cell lines recently found naturally generate episodic...
Abstract The APOBEC3 family of cytidine deaminases is widely speculated to be a major source somatic mutations in cancer 1–3 . However, causal links between enzymes and human cells have not been established. identity the paralog(s) that may act as prime drivers mutagenesis mechanisms underlying different APOBEC3-associated mutational signatures are unknown. To directly investigate roles mutagenesis, candidate genes were deleted from cell lines recently found naturally generate episodic...
Abstract Maintenance of telomeres in the absence telomerase is known as Alternative Lengthening Telomeres (ALT), which prevalent 10-15% all cancers. Tessellate BIO targets ALT mechanisms to drive cell death by synthetic lethality. To identify patients who will benefit from our therapy, we are developing companion diagnostics (CDx). In this study, established hallmarks investigated CDx target tissue-derived samples. fresh and FFPE tumor tissue, presence abundance different were measured,...