• It is not clear whether Rad1, Rad9 and Hus1 also have distinct functional activities independent of the heterotrimeric form. (biomedcentral.com)
  • Human Rad1 is a component of a heterotrimeric PCNA like complex that also contains the Rad9 and Hus1 proteins. (biossusa.com)
  • eukaryotic translational initiation aspect-2 kinase 3 (Benefit), inositol-requiring enzyme 1 (IRE1) and activating transcription aspect 6 (ATF6) thus activating these protein. (cgp60474.com)
  • Long term and extreme ER tension induced -cell apoptosis is certainly connected with c-jun N-terminal kinase (JNK) activation [9], [15]. (cgp60474.com)
  • Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor. (abcam.cn)
  • The presence of replication stress activates the DNA damage response and downstream checkpoint proteins including ataxia telangiectasia and Rad3 related kinase (ATR), checkpoint kinase 1 (CHK1), and WEE1-like protein kinase (WEE1), which trigger cell cycle arrest while protecting and restoring stalled replication forks. (bmj.com)
  • ATF4 activates the transcription of C/EBP homologous proteins (CHOP), considered to mediate palmitate-induced -cell loss of life [10], [11]. (cgp60474.com)
  • Eukaryotic cells have developed exquisite mechanisms that monitor and coordinate cell cycle progression with repair of DNA damage to maintain genome integrity. (biomedcentral.com)
  • Maintaining genomic integrity is of utmost importance to eukaryotic cells, which have evolved sophisticated mechanisms to ensure speed, accuracy, and an adequate pool of nucleotide and replication factors as well as high-fidelity repair pathways to correct errors occurring during DNA replication. (bmj.com)
  • The Rad1 protein, evolutionarily conserved from yeast to humans, exists in cells as monomer as well as a component in the 9-1-1 protein complex. (biomedcentral.com)
  • The S. cerevisiae checkpoint protein Rad17, the orthologue of human Rad1, forms a homocomplex in response to treatment with DNA damaging agents, and the complex is required for yeast survival after exposure to genotoxic agents [ 12 ]. (biomedcentral.com)
  • This complex is believed to be involved in cellular responses to DNA damage, possibly by associating with Rad17 and several components of the PCNA-loading heteropentamer, replication factor C. Human Rad1 exhibits significant homology to Rad1 from S. pombe, and its expression in yeast rad1 mutants has been shown to partially restore radiation resistance and G2 checkpoint activity. (biossusa.com)
  • Rad1 plays crucial roles in DNA repair and cell cycle checkpoint control, but its contribution to carcinogenesis is unknown. (biomedcentral.com)
  • To determine whether Rad1 functions to maintain genomic stability and prevent tumor development, we generated Mrad1 mutant mice by gene targeting. (biomedcentral.com)
  • It is likely that increased Rad9 expression is needed for proliferation of tumor cells by mechanisms such as getting beyond (tolerating) oncogene-induced replicative stress and enhancing DNA repair capability. (biomedcentral.com)
  • The ER tension response, also called the unfolded proteins response (UPR), is certainly a complicated signaling network initiated to revive regular ER homeostasis by lowering protein fill and increasing proteins folding capability. (cgp60474.com)
  • In the presence of errors or damage during DNA replication, cell cycle checkpoint nodes and repair machinery work in concert to retard cell cycle progression until sufficient repair has been achieved. (bmj.com)
  • Any obstacles encountered by cells in this process can lead to 'replicative stress' ( Figure 1 ), 1 which may be overcome by replicative stress response proteins, but deficiencies in this response result in accumulated errors in DNA replication and loss of genomic integrity, which lead to cell death. (bmj.com)
  • The effects of heterozygous deletion of Mrad1 on proliferation and apoptosis of keratinocytes is different from those resulted from Mrad9 heterozygous deletion (from our previous study), suggesting that Mrad1 also functions independent of Mrad9 besides its role in the Mrad9-Mrad1-Mhus1 complex in mouse cells. (biomedcentral.com)
  • Irradiated normal human fibroblasts (no reactivity against non-irradiated cell extracts). (abcam.cn)
  • Here we identified Nup2 in a pool of enriched proteins that co-purify with tagged Ndj1 from meiotic cell extracts. (biorxiv.org)
  • Knockdown of Rad9 in prostate tumor cells correlates with reduction of tumorigenicity in nude mice [ 16 ]. (biomedcentral.com)
  • Keratinocytes isolated from Mrad1 +/- mice had significantly more spontaneous DNA double strand breaks, proliferated slower and had slightly enhanced spontaneous apoptosis than Mrad1 +/+ control cells. (biomedcentral.com)
  • JNK1 shRNA expressing INS1 cells demonstrated elevated apoptosis and cleaved caspase 9 and 3 in comparison to nonsense shRNA expressing control INS1 cells when subjected to palmitate and high blood sugar associated with elevated CHOP appearance, ROS development and mRNA appearance. (cgp60474.com)
  • JNK2 shRNA expressing INS1 cells didn't influence palmitate and high blood sugar induced apoptosis or ER tension markers, but increased appearance in comparison to non-sense shRNA expressing INS1 cells mRNA. (cgp60474.com)
  • Finally, JNK3 shRNA expressing INS1 cells didn't induce apoptosis in comparison to nonsense shRNA expressing INS1 cells when subjected to palmitate and high blood sugar but showed elevated caspase 9 and 3 cleavage connected with elevated and mRNA appearance. (cgp60474.com)
  • These data claim that JNK1 protects against palmitate and high glucose-induced -cell apoptosis connected with decreased ER and mitochondrial tension. (cgp60474.com)
  • In proinflammatory cytokine-induced -cell apoptosis JNK activation is quite transient and rapid [20]. (cgp60474.com)
  • ER stress cross-talks to the mitochondrial or intrinsic death pathway via p53-upregulated modulator of apoptosis (Puma) and JNK-dependent upregulation of the Death protein (DP5) [27]. (cgp60474.com)
  • Obese and diabetic topics have raised plasma degrees of nonesterified essential fatty acids (NEFAs) and hyperglycemia, that are believed to trigger reduced insulin synthesis and impaired blood sugar responsiveness in pancreatic -cells, termed glucolipotoxicity [2] also, [3]. (cgp60474.com)
  • Each origin is initiated by a combination of regulatory proteins that prepare the chromatin for replication before synthesis (S)-phase entry. (bmj.com)
  • Nup2 is a nonessential nucleoporin that functions in nuclear transport, boundary activity, and telomere silencing in mitotically dividing cells. (biorxiv.org)
  • Small molecule inhibitors designed to target the DNA damage sensors, such as inhibitors of ataxia telangiectasia-mutated (ATM), ATR, CHK1 and WEE1, impair smooth cell cycle modulation and disrupt efficient DNA repair, or a combination of the above, have demonstrated interesting monotherapy and combinatorial activity, including the potential to reverse drug resistance and have entered developmental pipelines. (bmj.com)
  • The activity of the p53 gene product is regulated by a plethora of posttranslational modifications. (rupress.org)
  • Cells are constantly exposed to stresses from cellular metabolites as well as environmental genotoxins. (biomedcentral.com)
  • Meiosis is a specialized cellular program required to create haploid gametes from diploid parent cells. (biorxiv.org)
  • Strategies that increase replicative stress while lowering cell cycle checkpoint thresholds may allow unrepaired DNA damage to be inappropriately carried forward in replicating cells, leading to mitotic catastrophe and cell death. (bmj.com)
  • Store at -20°C. Aliquot into multiple vials to avoid repeated freeze-thaw cycles. (biossusa.com)
  • Shipped at 4°C. Upon delivery aliquot and store at -20°C or -80°C. Avoid repeated freeze / thaw cycles. (abcam.cn)
  • Besides the existence of 9-1-1 heterotrimer in K562 and 293 human cells, a significant amount of hRad1 also exists in monomeric form, but monomeric hRad9 and hHus1 were not detectable in a study by Karnitz's group [ 10 ] and in our unpublished experiments in 293 human cells. (biomedcentral.com)
  • Acknowledgments We thank Morten Lundh for exceptional sparring through the entire tests and Christopher Mayer for corporation using the steady cell lines. (cgp60474.com)
  • Abcam is leading the way in addressing this with our range of recombinant monoclonal antibodies and knockout edited cell lines for gold-standard validation. (abcam.cn)
  • This kinase has been shown to phosphorylate checkpoint kinase CHK1, checkpoint proteins RAD17, and RAD9, as well as tumor suppressor protein BRCA1. (genetex.com)
  • In addition, numerous reports have described an abnormal chromosomal phenotype affecting single or a few chromosomes in mitotic preparations from tumor-derived and other established cell lines. (prolekarniky.cz)
  • Furthermore, the under-condensed and late replicating phenotype present in tumor-derived cells occurred only on certain rearranged chromosomes and not on others, suggesting that the under-condensed and late replicating phenotype was associated with certain chromosomal rearrangements [5] . (prolekarniky.cz)
  • In yeast and mammalian cells commitment to enter S phase occurs during period in late G1 1, while commitment to enter mitosis 2 is indistinguishable from G2/M transition (for discussion see text). (comprehensivephysiology.com)
  • Morphological differences between mitotic chromosomes residing within the same cell were first described in mammalian cells over forty years ago (reviewed in [1] ). (prolekarniky.cz)
  • An alternatively spliced transcript variant of this gene has been reported, however, its full length nature is not known. (genetex.com)
  • In contrast to the transcript generated by an alternative splicing site in the intron 41, the one resulting from a deletion of 121 nucleotides in exon 33 is widely expressed, at significant but relatively low levels, in both normal and tumoral cells including normal breast and ovarian tissue. (biomedcentral.com)
  • Linkage studies in the 1990s led to the discovery of several predisposition genes associated with many rare familial cancer syndromes, thus providing fundamental insights into various pathways of carcinogenesis [ 4 ]. (biomedcentral.com)
  • The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (oncotarget.com)
  • Analyses of risk attributable to such alleles in the known breast cancer susceptibility genes (e.g. (biomedcentral.com)
  • If most cancer susceptibility is related to fundamental processes of cellular control, rare alleles might turn out to be the more important component and should be detectable by linkage analysis and/or the candidate gene re-sequencing approach [ 5 , 6 ]. (biomedcentral.com)
  • Disruption of ASAR6 results in delayed replication, delayed mitotic chromosome condensation, and activation of the previously silent alleles of mono-allelic genes on chromosome 6. (prolekarniky.cz)
  • Mutations of this gene are associated with Seckel syndrome. (genetex.com)
  • ATR appears as a good candidate breast cancer susceptibility gene and the current study was designed to screen for ATR germline mutations potentially involved in breast cancer predisposition. (biomedcentral.com)
  • Although no deleterious mutations were identified in the ATR gene, the current study provides an haplotype analysis of the ATR gene polymorphisms, which allowed the identification of a set of SNPs that could be used as tSNPs for large-scale association studies. (biomedcentral.com)
  • For cells, cell lines and tissues in culture till half confluency.Isotype or positive controls by peptides, antibodies and deactivated samples. (conzort.com)
  • Avoid multiple freeze-thaw cycles. (genetex.com)
  • In order to retain the quality and the affinity of productone unchanged, please, avoid cycles of freezing and thawing. (conzort.com)
  • ATR (phospho Thr1989) antibody detects ATR (phospho Thr1989) protein at nucleus by immunohistochemical analysis. (genetex.com)
  • Gliomas are the most common primary tumors that arise within the brain and have histologic features similar to normal glial cells (i.e., astrocytes, oligodendrocytes, and ependymal cells). (oncotarget.com)
  • SNP haplotypes were established and tSNPs were identified in 73 healthy unrelated French Canadians, providing a valuable tool for further association studies involving the ATR gene, using large cohorts. (biomedcentral.com)