H2AX phosphorylation is an early step in the response to DNA damage. It widely accepted that ATM (ataxia telangiectasia mutated protein) phosphorylates double-strand breaks (DSBs). Whether DNA-dependent protein kinase (DNA-PK) plays any role this unclear. Here, we show after exposure ionizing radiation (IR) occurs similar extents human fibroblasts and mouse embryo lacking either DNA-PK or but ablated ATM-deficient cells treated with LY294002, a drug specifically inhibits DNA-PK....

The tumor suppressor p53 binding protein 1 (53BP1) binds to the DNA-binding domain of and enhances p53-mediated transcriptional activation. 53BP1 contains two breast cancer susceptibility gene COOH terminus (BRCT) motifs, which are present in several proteins involved DNA repair and/or damage–signaling pathways. Thus, we investigated potential role Here, report that becomes hyperphosphorylated forms discrete nuclear foci response damage. These colocalize at all time points with...

p53 is a tumor-suppressor protein that can activate and repress transcription. Using the yeast two-hybrid system, we identified two previously uncharacterized human proteins, designated 53BP1 53BP2, bind to p53. shows no significant homology proteins in available databases, whereas 53BP2 contains adjacent ankyrin repeats Src 3 domain. In vitro binding analyses indicate both of these central domain (residues 80-320) required for site-specific DNA binding. Consistent with this finding, cannot...

p53 is a tumor suppressor protein that controls cell proliferation by regulating the expression of growth control genes. In previous study, we identified two proteins, 53BP1 and 53BP2, are able to bind wild type but not mutant via DNA-binding domain p53. We isolated cDNAs expressing full-length human clone, which predicts 1972 residues can be detected in H358 lung carcinoma line. The <i>53BP1</i> <i>53BP2</i> genes were mapped chromosomes 15q15–21 1q41–42, respectively. Immunofluorescence...

RIG-I is a DExD/H-box RNA helicase and functions as critical cytoplasmic sensor for viruses to initiate antiviral interferon (IFN) responses. Here we demonstrate that another DHX36 key molecule signaling by regulating double-stranded (dsRNA)-dependent protein kinase (PKR) activation, which has been shown be essential the formation of stress granule (avSG). We found PKR form complex in dsRNA-dependent manner. By forming this complex, facilitates dsRNA binding phosphorylation through its...

Upon DNA damage, p53-binding protein 1 (53BP1) relocalizes to sites of double-strand breaks and forms discrete nuclear foci, suggesting its role in damage responses. We show that 53BP1 changed localization from the detergent soluble insoluble fraction after treatment cells with x-ray, but not ultraviolet or hydroxyurea. Either DNase phosphatase released into fraction, showing binds chromatin a phosphorylation-dependent manner X-irradiation cells. was retained at foci X-irradiated even...

Human histone H2AX is rapidly phosphorylated on serine 139 in response to DNA double-strand breaks and plays a crucial role tethering the factors involved repair damage signaling. Replication stress caused by hydroxyurea or UV also initiates phosphorylation S-phase cells, although UV-induced non-cycling cells has recently been observed. Here we study human primary fibroblasts under growth-arrested conditions. This reaction absolutely depends nucleotide excision (NER) mechanistically distinct...

Recruitment of RAD18 to stalled replication forks facilitates monoubiquitination PCNA during S-phase, promoting translesion synthesis at sites UV irradiation-induced DNA damage. In this study, we show that is also recruited ionizing radiation (IR)-induced double-strand breaks (DSBs) forming foci which are co-localized with 53BP1, NBS1, phosphorylated ATM, BRCA1 and γ-H2AX. associates 53BP1 DSB in a 53BP1-dependent manner specifically G1-phase, monoubiquitinates KBD domain lysine 1268 vitro....

RBM8A (Y14) contains an RNA-binding motif and forms a tight heterodimer with Magoh. The is known to be member of the exon junction complex that on mRNA before export it required for metabolism processes such as splicing, nonsense-mediated decay. Recently, deficient cellular proliferation has been observed in RBM8A- or Magoh-depleted cells. These results prompted us study role cell cycle progression human tumour depletion A549 cells resulted poor survival accumulation mitotic After release...

Abstract Accumulating evidence indicates that transcription is closely related to DNA damage formation and the loss of RNA biogenesis factors causes genome instability. However, whether such are involved in responses remains unclear. We focus here on helicase Aquarius ( AQR ), a known R-loop processing factor, show its depletion human cells results accumulation during S phase, mediated by formation. investigated involvement found knockdown decreased damage-induced foci Rad51 replication...

Abstract The nucleus of mammalian cells is compartmentalized by nuclear bodies such as speckles, however, involvement bodies, especially in DNA repair has not been actively investigated. Here, our focused screen for speckle factors involved homologous recombination (HR), which a faithful double-strand break (DSB) mechanism, identified transcription-related potential HR regulators. Among the top hits, we provide evidence showing that USP42, hitherto unidentified speckles protein, promotes...

DNA topoisomerase II (Top2) induces double-strand breaks (DSBs) to relieve the torsional stress associated with replication and transcription. Etoposide (ETP), a Top2 poison in clinical use as an anticancer drug, traps reactive intermediates, resulting accumulation of DSBs, coupled formation Top2-DNA protein crosslinks (Top2-DPC) at ends DSBs. Proteasome-dependent processing trapped is necessary for some cellular responses ETP-induced DSBs; however, effect suppressing removal on DSB repair...

Ionizing radiation (IR) induces a variety of DNA lesions. The most significant lesion is double-strand break (DSB), which repaired by homologous recombination or nonhomologous end joining (NHEJ) pathway. Since we previously demonstrated that IR-responsive protein 53BP1 specifically enhances activity ligase IV, required for NHEJ, investigated responses 53BP1-deficient chicken DT40 cells to IR. showed increased sensitivity X-rays during G1 phase. Although intra-S and G2/M checkpoints were...

Centrosome amplification can be detected in the tissues of p53 −/– mice. In contrast, loss does not induce centrosome cultured human cells. However, examination cancer and cells has revealed a significant correlation between or mutational inactivation occurrence amplification, supporting notion that mutation alone is insufficient to cells, additional regulatory mechanisms are involved. It recently been shown gamma irradiation tumor induces amplification. precise mechanism radiation‐induced...

Nonhomologous end-joining (NHEJ) and homologous recombination (HR) are two major pathways for repairing DNA double-strand breaks (DSBs); however, their respective roles in human somatic cells remain to be elucidated. Here we show using a series of gene-knockout cell lines that NHEJ repairs nearly all the topoisomerase II- low-dose radiation-induced damage, while it negatively affects survival harbouring replication-associated DSBs. Intriguingly, find loss ligase IV, critical ligase, Artemis,...

The ubiquitously expressed β2-spectrin (β2SP, SPTBN1) is the most common non-erythrocytic member of β-spectrin gene family. Loss leads to defects in liver development, and its haploinsufficiency spontaneously chronic disease eventual development hepatocellular cancer. However, specific role homeostasis remains be elucidated. Here, we reported that was cleaved by caspase-3/7 upon treatment with acetaminophen which main cause acute injury. Blockage cleavage robustly attenuated...

&lt;i&gt;Objective:&lt;/i&gt; In order to elucidate the effects of radiation on centrosome hyperamplification (CH), we examined duplication cycle in KK47 bladder cancer cells following irradiation. &lt;i&gt;Methods:&lt;/i&gt; were irradiated with various doses and for CH immunostaining γ-tubulin. &lt;i&gt;Results:&lt;/i&gt; Nearly all control contained one or two centrosomes, mitotic displayed typical bipolar spindles. The replication is well regulated KK47. Twenty-four hours after 5-Gy...