• During meiotic recombination in human and mouse, CHEK1 protein kinase is important for integrating DNA damage repair with cell cycle arrest. (wikipedia.org)
  • In addition, we investigated several cell cycle-related proteins and found that co-knockdown of hTopBP1 and hMYH significantly diminished cell cycle arrest due to compromised checkpoint kinase 1 (Chk1) activation. (biomedcentral.com)
  • It also directly binds to BubR1, a kinetochore-associated kinase implicated in the mitotic checkpoint, the major cell cycle control pathway in which unattached kinetochores prevent anaphase onset. (rupress.org)
  • Thus, CENP-E is required for enhancing recruitment of its binding partner BubR1 to each unattached kinetochore and for stimulating BubR1 kinase activity, implicating it as an essential amplifier of a basal mitotic checkpoint signal. (rupress.org)
  • These genetic aberrations may cause loss of growth inhibition in normally quiescent cells and result in carcinogenesis [ 5 ]. (biomedcentral.com)
  • Importantly, etoposide and actinomycin D treatments increased histone H3K36 trimethylation in T/T, but not G/G cells, suggesting a G/G correlated inhibition of transcription elongation. (oncotarget.com)
  • Knockdown of Rad9 in prostate tumor cells correlates with reduction of tumorigenicity in nude mice [ 16 ]. (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)
  • To address this issue, primary mouse cells, haploinsufficient for one or two proteins, ATM and RAD9, related to the cellular response to DNA damage were examined. (aacrjournals.org)
  • The results show that cells having low levels of both ATM and RAD9 proteins are more sensitive to transformation by radiation, have different DNA double-strand break repair dynamics and are less apoptotic when compared with wild-type controls or those cells haploinsufficient for only one of these proteins. (aacrjournals.org)
  • Our conclusions are that under stress conditions, the efficiency and capacity for DNA repair mediated by the ATM/RAD9 cell signaling network depend on the abundance of both proteins and that, in general, DNA repair network efficiencies are genotype-dependent and can vary within a specific range. (aacrjournals.org)
  • These DNA breaks must be repaired before metaphase I. and these DSBs must be repaired before metaphase I. The cell monitor these DSBs via ATM pathway, in which Cdc25 is suppressed when DSB lesion is detected. (wikipedia.org)
  • This pathway is the same as classical DNA damage response and is the part we know the best in meiotic recombination checkpoint. (wikipedia.org)
  • The DSB-independent pathway was proposed when people studied spo11 mutant cells in some species and found that these Spo11 cells could not process to metaphase I even in the absence of DSB. (wikipedia.org)
  • Here, we report a critical role for the Trp53-Trp53inp1-Tnfrsf10b pathway during radiation-induced SSC apoptosis. (bvsalud.org)
  • Although Bbc3, a member of the intrinsic apoptotic pathway, was implicated in apoptosis of germ and somatic stem cells, Bbc3 depletion inhibited apoptosis in committed spermatogonia, but not in SSCs. (bvsalud.org)
  • Human DNA topoisomerase II-binding protein 1 (hTopBP1) plays an important role in DNA replication and the DNA damage checkpoint pathway. (biomedcentral.com)
  • The ataxia telangiectasia and Rad3-related protein (ATR) signaling cascade is an important pathway involved in the checkpoint control mechanism [ 3 ]. (biomedcentral.com)
  • Thus, hTopBP1 constitutes an important part of the ATR signaling pathway and acts as a molecular bridge that associates the independently recruited 9-1-1 and ATR-ATRIP complexes, thereby leading to checkpoint activation [ 4 ]. (biomedcentral.com)
  • Chemotherapeutic agents that damage DNA activate the p53 pathway and can initiate cancer cell death [ 1 , 2 ]. (oncotarget.com)
  • Immunoblotting with and without dephosphorylation was used to define the protein isolated from breast cancer cells. (biomedcentral.com)
  • Increased hRad9 protein was observed in breast cancer cells nucleus compared to non-tumor epithelium. (biomedcentral.com)
  • To further examine the role of hRad9 in breast cancer cells, we now report on the histologic expression of the hRad9 protein and its different molecular forms in primary breast cancer and normal tissues. (biomedcentral.com)
  • Conversely the dynamin-related protein 1 (Drp1/DNM1) is definitely a cytosolic protein recruitment of which to the OMM from the anchored fission 1 protein (Fis1p/FIS1) adaptor initiates and settings the fission and distribution of mitochondria in cells [19]. (tech-strategy.org)
  • 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)
  • The accumulation of hTopBP1 on chromatin and its subsequent interaction with hRad9 lead to cell cycle arrest, a process mediated by Chk1 phosphorylation and ataxia telangiectasia and Rad3-related protein (ATR) activation. (biomedcentral.com)
  • Human DNA topoisomerase II-binding protein 1 (TopBP1) and its orthologs play important roles in DNA replication and checkpoint control [ 1 ]. (biomedcentral.com)
  • Because the effect of haploinsufficiency for one protein is relatively small, we hypothesize that predisposition to cancer could be a result of the additive effect of heterozygosity for two or more genes, critical for pathways that control DNA damage signaling, repair or apoptosis. (aacrjournals.org)
  • In addition HIV-1 Vpr protein alters the cell-cycle regulation by hijacking centrosome functions. (biomedcentral.com)
  • It forms a checkpoint protein complex with RAD1 and HUS1. (avivasysbio.com)
  • This complex is recruited by checkpoint protein RAD17 to the sites of DNA damage, which is thought to be important for triggering the checkpoint-signaling cascade. (avivasysbio.com)
  • The special chromosome separation in meiosis, homologous chromosomes separation in meiosis I and chromatids separation in meiosis II, requires special tension between homologous chromatids and non-homologous chromatids for distinguishing microtubule attachment and it relies on the programmed DNA double strand break (DSB) and repair in prophase I. Therefore meiotic recombination checkpoint can be a kind of DNA damage response at specific time spot. (wikipedia.org)
  • Normally, structural damage of DNA by endogenous and environmental agents is followed by replication checkpoint arrest at the G2/M transition in order to allow for repair before proceeding in the cell cycle. (biomedcentral.com)
  • This event is triggered by the activation of M-Cdk in late prophase I. Then the spindle assembly checkpoint examines the attachment of microtubules at kinetochores, followed by initiation of metaphase I by APCCdc20. (wikipedia.org)
  • The anti-apoptotic Bcl-2 relative Bcl-xL as well as the antagonist BH3 just proteins Bak/Bax had been proven to regulate mitochondrial form in healthful cells aswell such as cells going through apoptosis [13] [14]. (tech-strategy.org)
  • Finding of hyperphosphorylated forms of hRad9 in the nucleus of cancer cells is in keeping with its function in ameliorating DNA instability, whereby it inadvertently assists tumor growth. (biomedcentral.com)
  • Thus, in addition to its checkpoint control function, hRad9 may play a role in regulating apoptosis. (biomedcentral.com)
  • 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)
  • hTopBP1 and hMYH were involved in ATR-mediated Chk1 activation, moreover, both of them were associated with ATR and hRad9 which known as checkpoint-involved proteins. (biomedcentral.com)
  • Structure-guided point mutations in either CAPN7 MIT domain disrupted IST1 binding in vitro and in cells, and depletion/rescue experiments showed that the CAPN7-IST1 interaction is required for: 1) CAPN7 recruitment to midbodies, 2) efficient abscission, and 3) NoCut checkpoint arrest. (elifesciences.org)
  • One of the oxidative DNA lesions frequently generated upon exposure of cells to reactive oxygen species (ROS) is 7,8-dihydro-8-oxoguanine (8-oxoG) [ 13 ]. (biomedcentral.com)
  • Genomic instability caused by mutation of the checkpoint molecule TP53 may endow cancer cells with the ability to undergo genomic evolution to survive stress and treatment. (biomedcentral.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)
  • Journal of Cell Biology, 83 (2 PART). (cshl.edu)
  • Journal of Cell Biology, 95 (2). (cshl.edu)
  • Molecular Biology of the Cell, 19 (7). (cshl.edu)
  • Nature Cell Biology, 9 (5). (cshl.edu)
  • a connection between mitochondrial function and dynamics in the legislation of fat burning capacity cell loss of life neurotransmission cell routine control and advancement [15]. (tech-strategy.org)
  • Rad1 plays crucial roles in DNA repair and cell cycle checkpoint control, but its contribution to carcinogenesis is unknown. (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)
  • They localize in close proximity to the nucleus for the duration of interphase and play major roles in numerous cell functions. (biomedcentral.com)
  • We previously showed that the ESCRT-III subunit IST1 binds the cysteine protease CAPN7 (Calpain-7) and that CAPN7 is required for both efficient abscission and NoCut checkpoint maintenance (Wenzel <i>et al. (elifesciences.org)
  • Cells are constantly exposed to stresses from cellular metabolites as well as environmental genotoxins. (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)
  • Germ cells are thought to exhibit a unique DNA damage response that differs from that of somatic stem cells, and previous studies suggested that Trp53 is not involved in the survival of spermatogonial stem cells (SSCs) after irradiation. (bvsalud.org)
  • The Endosomal Sorting Complexes Required for Transport (ESCRT) machinery mediates the membrane fission step that completes cytokinetic abscission and separates dividing cells. (elifesciences.org)
  • The meiotic recombination checkpoint monitors meiotic recombination during meiosis, and blocks the entry into metaphase I if recombination is not efficiently processed. (wikipedia.org)
  • Centrosome duplication is tightly regulated and limited at once per cell cycle through a mechanism that prevents re-duplication. (biomedcentral.com)
  • In conclusion for cancer cells overexpressing MDM2, targeting MDM2 may be less effective than inducing p53-independent cell death. (oncotarget.com)
  • We hypothesized that MDM2 in these cells inhibited transcription initiation at the p53 target genes p21 and puma . (oncotarget.com)
  • Surprisingly, following etoposide treatment transcription initiation occurred at the compromised target genes in MANCA and A875 cells similar to the T/T ML-1 cell line. (oncotarget.com)
  • We found that knockdown of MDM2 in G/G cells moderately increased expression of subsets of p53 target genes without increasing p53 stability. (oncotarget.com)
  • Presumably the C-terminal domain is essential for transport of the 9-1-1 complex from the cytoplasm into the nucleus, for activation of the G2 checkpoint signalling cascade [ 12 ]. (biomedcentral.com)
  • Centrosomes were first described at the end of the 19th century by Theodor Boveri who had also the intuition of their central role in cell life [ 1 ]. (biomedcentral.com)
  • These filaments also bind and recruit cofactors whose activities help execute abscission and/or delay abscission timing in response to mitotic errors via the NoCut/Abscission checkpoint. (elifesciences.org)
  • Background Mitochondria are central towards the fat burning capacity of cells and take part in many signaling and regulatory occasions. (tech-strategy.org)
  • Here, we leverage a set of genome-edited human PLIN2 reporter cell lines in a series of CRISPR-Cas9 loss-of-function screens, identifying genetic modifiers that influence PLIN2 expression and post-translational stability under different metabolic conditions and in different cell types. (stanford.edu)