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Showing 1 to 20 of 34 for “"53BP1"”.
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53BP1/Shieldin Counteract DSB Resection Through Fill-In Synthesis
<p>53BP1 is a DNA damage response (DDR) factor that gained notoriety because it determines the efficacy of PARP1 inhibitors (PARPi) in BRCA1-deficient cancers. Additionally, 53BP1 promotes end-to-end fusions of telomeres lacking end protection from the shelterin component TRF2, and facilitates …
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The Role of 53BP1 in DNA Double-Strand Break Repair
… Among DNA damage response factors, absence of 53BP1 leads to the most severe defect in CSR. Similarly, the loss of 53BP1 leads to impaired joining of distal DSBs during V(D)J recombination and results in abrogated transchromosomal fusions of dysfunctional telomeres. Interestingly, joining of …
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53BP1 and double-strand break repair pathway choice in cancer
… The Tumour Protein P53 Binding Protein 1 (TP53BP1) gene product plays a central role in DSB repair pathway choice, promoting non-homologous end-joining (NHEJ) and counteracting homologous recombination (HR). As with all DNA damage response (DDR) proteins, cell-cycle regulation of 53BP1 is …
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A histone H4 code regulates 53BP1-mediated responses to DNA damage
… binding of the P53-binding protein 1 (53BP1) to dimethyl K20 H4 (K20me2) and the formation of 53BP1 nuclear foci near double strand breaks are early events in DNA damage responses (DDR) that provide a platform for the assembly of downstream effectors. Since global levels of K20me2 are …
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A New Pathway Responsible For 53BP1 Loss in Breast Cancer and Laminopathies
<p>53BP1 is a tumor suppressor protein that is important in the non-homologous end joining: NHEJ) pathway for DNA double strand break repair. Mice lacking 53BP1 present with increased radiosensitivity and genomic instability and are cancer prone. Loss of 53BP1 has been implicated by our laboratory …
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RNA-MEDIATED PHASE SEPARATION OF 53BP1: CONNECTING CONDENSATE BIOPHYSICS TO DNA DAMAGE RESPONSE
… Recently, we reported that among DDR components, 53BP1 accumulates at DNA damage sites in liquid-like foci, with RNA supporting this process and aiding the DNA repair pathway. However, mechanisms regulating 53BP1 condensation by RNA remain elusive. Here, we identify 53BP1 molecular determinants …
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Characterization of a Novel 53BP1-Dependent Mechanism that Promotes Non-Homologous End Joining of Deprotected Telomeres by Increasing Chromatin Mobility
… of DNA damage response factors (e.g. MDC1, 53BP1). Although several lines of evidence have pointed to a role for some of these factors in DSB repair through non-homologous end-joining (NHEJ), the mechanism of their contribution has not been established. To study the regulation of NHEJ, we …
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Pathways of NHEJ at Dysfunctional Telomeres and Their Resolution
… is focused on the DNA damage response factor 53BP1, a key regulator in double strand break (DSB) repair pathways in mammalian cells. By influencing key regulatory events at and near DNA ends, 53BP1 plays an important role in the decision between non-homologous endjoining (NHEJ) and homologous …
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The interaction of CtIP with DNA damage response proteins
… mediator proteins containing BRCT domains: 53BP1, MDC1, TopBP1 and NBS1. The binding sites on all of these proteins have been mapped establishing which regions of CtlP interact directly with 53BP1, MDC1, TopBP1 and NBS1 and vice versa. This implies that CtlP is involved in the DNA damage …
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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
… an unusual sensitivity to aphidicolin: 25-28% of 53BP1 foci induced by aphidicolin treatment colocalized with telomeric DNA. Expression of TRF2 S366E improved survival of MEFs after aphidicolin treatment. Cells expressing TRF2 S366E also exhibited fewer chromatid breaks and 53BP1 foci after …
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Space radiation-induced bystander signaling in 2D and 3D skin tissue models
… of foci of the DNA repair-related protein 53BP1. In the 2D system, both protons and iron ions yielded a strong dose dependence for the induction of 53BP1 in irradiated cells, while the magnitudes and time courses of bystander responses were dependent on radiation quality. Furthermore, …
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THE DNA DAMAGE CHECKPOINT REGULATES MISMATCH REPAIR COMPLEXES DURING SINGLE STRAND ANNEALING PATHWAY
… limits the binding of the DDC mediator Rad9/53BP1 in proximity of the DSB, reducing checkpoint signalling. We observed that the deletion of RAD9 gene rescues the defects in SSA of both rad1Δ and slx4Δ mutant cells. Therefore, we hypothesized that the DDC limits the activity of a nuclease …
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The Adenylate-Uridylate-Rich element RNA binding protein ZFP36L1 suppresses replication stress-induced genomic instability
… by increased γH2AX foci colocalising with 53BP1. Surprisingly, chromatin enrichment of U-2OS, HCT116 and Hela cells demonstrated that ZFP36L1 is physically bound to chromatin fractions. Here we also demonstrated the specificity of CRISPR-Cas9 mediated ablation of ZFP36L1 through the …
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p53 Functional Interactions: the Study of a New Crosstalk with Estradiol Pathway in Transcriptional Responses to Chemotherapeutics
… positive and negative cofactors (e.g. MDM4 and 53BP1) and the impact of small molecules, including chemotherapeutic drugs, on such interactions. Previous reports have revealed a complex, often negative, crosstalk between p53 and estrogen receptors (ERs) related in part to the physical …
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The Role of ZMYND8 in Immunoglobulin Class Switch Recombination
… (NHEJ). Critical components of CSR are 53BP1 and its effector RIF1 because they inhibit end resection to promote NHEJ and oppose competing pathways in DDR. However, the mechanism by which RIF1 effects end-protection in CSR and binds to 53BP1 is still unknown In these studies, I …
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Identification of Epstein-Barr virus proteins that inhibit the DNA damage response
… the ability to interfere with the formation of 53BP1 foci, a late step in the DDR, in response to etoposide-induced DNA damage. An uncharacterized tegument protein, BKRF4, was identified as an inhibitor of the DNA damage response. By studying the effect of BKRF4 on the steps of the DDR, it was …
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Post-Replicative Resolution of Under-Replication
… The number of ultrafine anaphase bridges and 53BP1 nuclear bodies are in remarkable concordance with the theoretical predictions for the number of double fork stalls, indicating that cells are able to tolerate under-replication through such post-replicative cellular responses. 53BP1 …
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Novel Roles for A-Type Lamins in Maintaining Genomic Stability
… maintain post-translational stabilization of 53BP1, which is an important NHEJ protein. In addition, A-type lamins maintain HR by regulating transcription of BRCA1 and RAD51, two essential HR factors. Importantly, the study of A-type lamins has led us to the discovery of a cysteine protease, …
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PIKK-dependent activation of the DNA damage response by long wavelength ultraviolet radiation
… suggesting a greater dependence on ATM activity. 53BP1 foci formation was used to investigate NHEJ activation. There was a significant increase in the number of UVA-induced 53BP1 foci, while the addition of an ATM inhibitor prevented this increase, suggesting an ATM dependence for NHEJ activation. …
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Identification and Characterization of the DNA Damage Response Function of Human Rif1 and a Search For Human Rap1 Interacting Factors
… with other DNA damage response factors such as 53BP1, ATM, BRCA1, Chkl, Nbsl, and Rad 17. Furthermore, Rifl localized to uncapped telomeres, as do other DNA damage response factors. Among DNA damage response proteins, Rifl showed a unique dependence on the ATM kinase. Whereas inhibition of ATR …
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