نتایج جستجو برای: h2ax gene
تعداد نتایج: 1142668 فیلتر نتایج به سال:
Background/Aim: Poly (ADP-ribose) polymerase inhibitors (PARPis) are one of the targeted therapies proven to treat breast cancer gene (BRCA)-mutant ovarian cancer. Because most cancers BRCA wild-type, it is necessary extend usage PARPis. In present study, we combined PARPi, talazoparib, and IL-6 inhibitor, bazedoxifene, for treatment human cells. Materials Methods: The cell lines, SKOV3, UWB1.2...
Chromatin reorganization plays an important role in DNA repair, apoptosis, and cell cycle checkpoints. Among proteins involved in chromatin reorganization, TIP60 histone acetyltransferase has been shown to play a role in DNA repair and apoptosis. However, how TIP60 regulates chromatin reorganization in the response of human cells to DNA damage is largely unknown. Here, we show that ionizing irr...
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and are caused by activating mutations of the KIT or platelet-derived growth factor receptor alpha (PDGFRA) tyrosine kinases. GISTs can be successfully treated with imatinib mesylate, a selective small-molecule protein kinase inhibitor that was first clinically approved to target the onc...
A crucial event in the DNA damage response is the phosphorylation and subsequent ubiquitination of H2AX, required for the recruitment of proteins involved in DNA repair. Here we identify a novel regulator of this process, the ubiquitin hydrolase Dub3. Overexpression of wild type, but not catalytic inactive, Dub3 decreases the DNA damage-induced mono-ubiquitination of H2A(X) whereas downregulati...
The DNA double-strand break (DSB) is the primary lethal lesion after therapeutic radiation. Thus, the development of assays to detect and to quantitate these lesions could have broad preclinical and clinical impact. Phosphorylation of histone H2AX to form gamma-H2AX is a known marker for irradiation-induced DNA DSBs. However, the first generation assay involves the use of immunofluorescent stai...
PURPOSE 2-Methoxyestradiol (2ME), an estrogen metabolite, induces apoptosis in various cell types. We investigated whether 2ME pretreatment can radiosensitize colon adenocarcinoma cells. EXPERIMENTAL DESIGN Radiosensitizing effects of 2ME were evaluated by cell death, clonogenic assay, nuclear fragmentation, and tumor progression of xenografts. Ionizing radiation-induced DNA damage was evalua...
Protein Tyrosine Kinase 6 (PTK6) is a non-receptor–type tyrosine kinase known to be expressed in various cancers, including pancreatic cancer. The role of PTK6 in cancer chemoresistance remains unclear. Therefore, it was hypothesized that PTK6 mechanistically regulates gemcitabine resistance in pancreatic cancer. Gemcitabine treatment stimulated endogenous PTK6 overexpression inMIAPaCa2 and Pan...
We have recently reported that topoisomerase 1 (Top1) cooperates with ASF/SF2, a splicing factor of the SR family, to prevent unscheduled replication fork arrest and genomic instability in human cells. Our results suggest that Top1 execute this function by suppressing the formation of DNA-RNA hybrids during transcription, these so-called R-loops interfering with the progression of replication f...
The DNA damage response (DDR) is crucial for genomic integrity. BRIT1 (breast cancer susceptibility gene C terminus-repeat inhibitor of human telomerase repeat transcriptase expression), a tumor suppressor and early DDR factor, is recruited to DNA double-strand breaks (DSBs) by phosphorylated H2A histone family, member X (γ-H2AX), where it promotes chromatin relaxation by recruiting the switch/...
Rapid phosphorylation of histone variant H2AX proximal to DNA breaks is an initiating event and a hallmark of eukaryotic DNA damage responses. Three mammalian kinases are known to phosphorylate H2AX in response to DNA damage. However, the mechanism(s) for damage-localized phosphorylation remains incompletely understood. The DNA-dependent protein kinase (DNA-PK) is the most abundant H2AX-modifyi...
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