Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
Results
Showing 1 to 20 of 71 for “"replication stress"”.
-
Establishing DNA combing to investigate DNA replication stress in vitro
… 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 replication by a variety of …
-
ZSCAN4 AND REPLICATION STRESS: SAFEGUARDING GENOME STABILITY IN MOUSE EMBRYONIC STEM CELLS
The accuracy of DNA replication is essential for maintaining genome stability. However, replication can be disrupted by both endogenous and exogenous factors, leading to a condition known as replication stress (RS). RS slows down and eventually stalls replication forks. If stalled forks are not …
-
THE IMPACT OF REPLICATION STRESS ON THE EPIGENOME OF MOUSE EMBRYONIC STEM CELLS
… marks are faithfully inherited during DNA replication through tightly coordinated processes. Our recent work demonstrated that disruption of DNA replication, known as replication stress, can expand the cell fate of mouse embryonic stem cells (mESCs) by activating totipotency and …
-
Multi-Omics Investigation to on the Effect of Replication Stress on Leukemia Cells
… line K562. Like AML lines studied previously, replication stress leads cells to adopt a cell state similar to oncogene knockdown. Replication stress is likely not acting through chromatin state directly given that upregulated genes did not vary in their H3K27 modification or polymerase pausing, …
-
The Adenylate-Uridylate-Rich element RNA binding protein ZFP36L1 suppresses replication stress-induced genomic instability
… as a newly identified cancer driver gene. Replication stress (RS) threatens DNA replication fidelity and stability of the genome. Recently, a small number of AU-RBPs have emerged as key figures in the maintenance of genome integrity through mechanisms that govern the replication stress …
-
Interrogating DNA replication stress and DNA damage responses via phenotypic and functional CRISPR/Cas9 screens
… ATM prevents toxic end- joining of broken replication forks. Inactivation of NHEJ or increased end-resection in the absence of BRCA1-A supresses toxic end-joining, thus enabling cellular survival in the presence of topotecan. Additionally I describe that the end-resection defect of BRCA1- …
-
The Role of the RNA-binding Protein ZFP36L1 in Suppression of Replication Stress-induced Genomic Instability
Replication stress, a hallmark of pre-cancerous and cancerous lesions, is characterised by the slowing or stalling in replication fork progression and the consequent failure to preserve genomic stability. ZFP36L1, a member of the ZFP36 family of CCCH tandem zinc finger (ZF) proteins, is an …
-
DEVELOPMENT OF 4'-ETHYNYL-2'-DEOXYCYTIDINE (EdC), A REPLICATION-STRESS INDUCING NUCLEOSIDE ANALOG PRODRUG WITH PREFERENTIAL ACTIVITY IN LEUKEMIA AND LYMPHOMA SUBTYPES
… phosphorylation for its activity and induces replication fork arrest and accumulation of cells in S-phase, indicating it acts as a chain terminator. A 2.1Å co-crystal structure of dCK bound to EdC and UDP reveals how the rigid 4’-alkyne of EdC fits within the active site of dCK. Remarkably, …
-
A Novel Phosphorylation Site in the Telomeric Protein TRF2 is Regulated by the ATR Kinase and Plays a Role in Relieving Replication Stress at the Telomere
… that phosphorylation of TRF2 on S368 may relieve replication stress at the telomere by modifying the conformation of shelterin to allow the replication fork to more easily pass.</p>
-
DDI1/2 and RTF2-Dependent Regulation of RNASE H2 at the Replisome Ensures Genome Stability
… DNA Damage Inducible 2 (DDI2), are active in the replication stress response (Kottemann et al., 2018). Under conditions of replication stress, DDI1/2 function to remove Replication Termination Factor 2 (RTF2) from the replisome. Persistence of RTF2 at the replisome compromises the replication …
-
Analysis of Meiotic Cancer Testis Antigens and Their Contribution to Tumorigenesis
… 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 mediated by the MRE11-DNA2-BLM …
-
Uncovering Phosphorylation Circuitries that Control DNA Replication Fork Dynamics
… genetic information to the daughter cell. DNA replication is a fundamental process that frequently encounters challenges from exogenous and endogenous sources. Barriers to replication slow down DNA synthesis and threaten the genetic integrity and viability of the cell. Cells are equipped with …
-
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 provide a …
-
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, FL-cycE …
-
Functions of RTF2 in DNA Replication and Checkpoint Control
… has uncovered one such dynamic process at replication forks experiencing replication stress, by which proteasome shuttle proteins DNA damage inducible 1 and DNA damage inducible 2 (DDI1/2) regulate the level of replication termination factor 2 (RTF2) at the replisome. When RTF2 is retained …
-
ATR SIGNALING IN GENOME REPLICATION AND MAINTENANCE
DNA replication is essential for cell survival. During DNA replication, cells encounter many challenges, such as dNTP depletion, transcription intermediates, chemical adducts, double strand breaks, and heterochromatin. Replication stress induced by these challenges activates the sensor kinase ATR …
-
Elucidation and characterisation of checkpoint kinase interactions with the replisome
… copied in each cell cycle by the process of DNA replication. During replication, cells must endure assaults from a myriad of exogenous and endogenous agents and events which can interfere with replication. Cells have evolved a surveillance mechanism called the DNA replication checkpoint (DRC) …
-
Genome-wide CRISPR Screening in FBXW7-mutant Cells Uncovers Multiple Druggable Synthetic Lethal Interactions Involving Cell Cycle Control
… response genes. We identified high levels of replication stress in FBXW7-/- cells and organoids, resulting in increased sensitivity to an inhibitor of the ATR kinase - a mediator of the cellular response to replication stress. We hypothesize that activation of DNA damage response in FBXW7-/- …
-
Mechanistic Understanding of the Role of TRF1 in Telomere Replication
… subunit TRF1 is important for facilitating the replication of telomeric DNA. Deletion of TRF1 results in several phenotypes that are thought to be associated with telomere replication stress, including ATR signaling, fork stalling, sister telomere associations, and fragile telomeres. Fragile …
-
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 other …
Page 1 of 4