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Showing 1 to 12 of 12 for “"DNA replication stress"”.
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Establishing DNA combing to investigate DNA replication stress in vitro
… cell cycle cells faithfully replicate their DNA utilizing multiple DNA replication sites known as origins of replication. DNA is replicated to provide each daughter cell a complete copy of the genome. Replication proceeds bi-directionally from a minority of potential origins licensed for …
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Interrogating DNA replication stress and DNA damage responses via phenotypic and functional CRISPR/Cas9 screens
DNA double-strand breaks are believed to be one of the most cytotoxic DNA lesions, posing a constant threat for genome integrity and cell survival. Consequently, various DNA repair processes and pathways have evolved to deal with different DNA lesions and ensure genome stability. The tumour …
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Analysis of Meiotic Cancer Testis Antigens and Their Contribution to Tumorigenesis
… roles in cell survival, modulating response to DNA damaging agents, and DNA replication stress mitigation respectively. More specifically, we find HORMAD1 is critical for protecting stalled DNA replication forks in LUAD. Loss of HORMAD1 leads to nascent DNA degradation, an event which is …
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Characterisation of non-essential genes required for survival under conditions of DNA stress
… to threats to the genome. This can lead to DNA replication stress and the potential loss of genetic integrity of the newly formed cells. The study of the sophisticated systems of DNA replication has been an attractive area for research in human and cancer, yet, the results do not fully …
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Metabolic and genetic factors guiding hematopoietic cell fate
… cell state changes specifically by impairing DNA replication, rather than as a general consequence of impaired proliferation or reduced viability. Genetic screens in three cell types reveal that while different cellular contexts have divergent responses to depletion of metabolic enzymes and …
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Molecular Characterization of Novel Mutations in Fanconi Anemia Patients
… proteins are required for the proper repair of DNA interstrand crosslinks (ICL), a deleterious type of DNA damage that covalently binds DNA strands. We have used Whole Exome Sequencing (WES) in conjunction with cell-based assays to determine disease-causing mutations in a subset of patients …
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ONCOGENE-INDUCED ALTERED DNA REPLICATION DYNAMICS
… cycle permanently. OIS results from a robust DNA damage response (DDR) activation due to oncogene-induced hyper-proliferation. By performing a whole genome analysis of DNA replication dynamics occurring upon oncogene activation, I discovered that oncogene activation alters DNA replication by …
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A Neural Network and Genome Language Model Based Approach to Understanding DNA Replication in Cancer
… identical daughter cells. This process is called DNA replication. DNA replication differs between healthy cells and cancer cells and can be exploited as a therapeutic target. At the same time, altered replication dynamics are critical for understanding cancer onset, evolution and treatment …
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Optimisation of TrAEL-seq to study DNA damage and replication in complex and dynamic mammalian cell systems
… evolved a complex set of mechanisms to ensure DNA is repaired and correctly replicated before cell division. Deficiencies in these repair pathways are heavily associated with the development of cancer and ageing, and it is therefore of interest to be able to detect and monitor the distribution …
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Understanding the activation mechanism of the Chk1 kinase
Faithful replication of DNA and correct segregation of duplicated chromosomes into two daughter cells are essential to ensure genome integrity and cell survival. Genome integrity is constantly threatened by endogenous and exogenous sources of DNA damage. Consequently, eukaryotic cells have evolved …
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Low Molecular Weight Cyclin E Deregulates Dna Replication and Damage Repair to Promote Genomic Instability In Breast Cancer
… promotes genomic instability by deregulating DNA replication and damage repair. We generated immortalized pre-cancerous human mammary epithelial cells (hMECs) engineered to express doxycycline inducible LMW-E or FL-cycE in <em>CCNE1</em> knock-out background. We found that, unlike LMW-E, …
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UNRAVELING THE MOLECULAR MECHANISM OF BRCA2-POLTETA INTERPLAY IN PREVENTING SSDNA GAP ACCUMULATION DURING DNA REPLICATION
DNA Polymerase theta (POLθ), encoded by POLQ, plays a critical role in alternative non-homologous end joining (alt-NHEJ), a backup pathway for repairing DNA double-strand breaks in the absence of homologous recombination. The synthetic lethal relationship between POLQ and BRCA1/2 has been …