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  • mitotic
  • The Rad24-RFC complex is involved in both the mitotic and meiotic checkpoints [ PMID: 10511543 ]. (ebi.ac.uk)
  • Curcumin treatment significantly increased the number of cells in M phase in 4 out of the 5 lines tested for this duration, and those with microsatellite instability (HCT116) were found to have a higher mitotic index than those with chromosomal instability. (core.ac.uk)
  • Pre-treatment with caffeine abrogated mitotic arrest in these cell lines, indicating the involvement of the ATM/ATR kinases. (core.ac.uk)
  • Furthermore, the high levels of pH2A.X staining seen in curcumin-treated mitotic but not interphase cells suggest that aberrant mitosis may result in DNA damage. (core.ac.uk)
  • 2004). Acute ablation of survivin uncovers p53-dependent mitotic checkpoint functions and control of mitochondrial apoptosis. (core.ac.uk)
  • Rad9
  • Moreover, we observed that hMYH was essential for the accumulation of hTopBP1 on damaged DNA, where hTopBP1 interacts with hRad9, a component of the Rad9-Hus1-Rad1 complex. (beds.ac.uk)
  • More specifically, the two major areas of current focus are the function and regulation of checkpoint mediators (Rad9/53BP1) and PIK kinases, (Mec1/ATR and ATM). (nuigalway.ie)
  • chromatin
  • The CCB currently consists of ten laboratory heads who direct over 80 full time researchers engaged in studies related to the function and regulation of checkpoints, centromeres, centrosomes, chromatin, DSB repair, DNA synthesis, nucleoli, trans lesion DNA synthesis and telomeres. (nuigalway.ie)
  • genome stability
  • Human OB-fold containing proteins are essential for multiple aspects of genome stability maintenance. (biomedcentral.com)
  • In 2001, he was appointed to the Chair of Biochemistry at the National University of Ireland Galway and founded the Genome Stability Laboratory, which focuses on the mechanisms of sensing and responding to DNA damage using yeast and vertebrate cells. (nuigalway.ie)
  • Genetic
  • However, utilization of an ectopic homologous sequence is a venturesome issue in regard to genetic stability and can occasionally result in genome rearrangements or loss of heterozygosity in diploid cells. (embopress.org)
  • This important choice has been shown to be under genetic control and regulated by FANCD2, which binds to DNA lesions and recruits repair proteins. (wormbook.org)
  • multiple proteins
  • Among these targets, CHK1 seems to be the most suitable target for therapeutic G 2 abrogation to date, although an unexplored target such as 14-3-3 or the strategy of targeting multiple proteins at once may be of interest in the future. (aacrjournals.org)
  • mouse embryonic
  • NIH3T3 cells (mouse embryonic fibroblast) were cultured in DMEM supplemented with 10% calf serum at 37°C in 10% CO 2 . (aacrjournals.org)
  • This reduction in digesting of Gluc in DYT1 cells may actually occur at least partly from a lack of torsinA activity because mouse embryonic fibroblasts missing torsinA also acquired reduced secretion in comparison with control cells. (desafioceroaedes.com)
  • This were due to decreased function of torsinA Fasudil HCl as an ER chaperone proteins because mouse embryonic fibroblasts (MEFs) from homozygous torsinA knockout mice also demonstrated decreased Gluc secretion in comparison with MEFs from wild-type and heterozygous littermates. (desafioceroaedes.com)
  • damage induced
  • Consistent with Spy1 having a role in the DNA damage response, endogenous Spy1 protein levels are up-regulated in response to DNA damage induced by camptothecin, cisplatin, or hydroxyurea. (aacrjournals.org)
  • topoisomerase
  • Many of the conventional anticancer treatments (including: ionizing radiation, hyperthermia, pyrimidine and purine antimetabolites, alkylating agents, DNA topoisomerase inhibitors, and platinum compounds) at least partly damage the DNA of cells. (aacrjournals.org)
  • hRAD9
  • 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. (beds.ac.uk)
  • HRAD9 also functions as a cell death mediator. (aacrjournals.org)
  • However, the precise molecular mechanisms involved in HRAD9-mediated signal transduction and the relationship to the proapoptotic activity of the protein remain unknown. (aacrjournals.org)
  • MEC1
  • To identify all putative SCD-containing proteins, we analyzed the distribution of S/T-Q motifs within verified Tel1/Mec1 targets and arrived at a unifying SCD definition of at least 3 S/T-Q within a stretch of 50 residues. (biomedcentral.com)
  • telomere
  • Besides checkpoint activation, Rad24 is also involved in double-strand break ends processing, DNA repair and telomere maintenance [ PMID: 12944484 , PMID: 11267834 , PMID: 10675560 , PMID: 15454530 ]. (ebi.ac.uk)
  • Although the GCRs induced by treatment with DNA-damaging agents were not reduced by rad1 or rad10 mutations, the translocation- and deletion-type GCRs created by a single double-strand break are mostly replaced by de novo telomere-addition-type GCR. (genetics.org)
  • mechanisms of cell cycle
  • Professor Lowndes is an expert on the mechanisms of cell cycle control and the DNA damage-response, a thorough understanding of which will translate into improved cancer diagnosis and therapeutic regimes. (nuigalway.ie)
  • repair
  • Efforts have been made to sensitize cancer cells specifically to these treatments since the late 1960s with compounds such as caffeine ( 1 ), which at the time was thought to directly inhibit the repair machinery. (aacrjournals.org)
  • The Saccharomyces cerevisiae DNA damage checkpoint is required for efficient repair of double strand breaks by non-homologous end joining. (ebi.ac.uk)
  • This in turn might recruit other proteins to DNA, perhaps serving as a signal to the cell cycle machinery or to facilitate repair. (aacrjournals.org)
  • Alternatively, the checkpoint response can be activated indirectly through recognition of repair intermediates that are generated by MMR. (pnas.org)
  • germ
  • The abundance of HRAD9B RNA, as judged by quantitative reverse transcription-PCR, is very low in most testicular tumors, particularly those of germ cell origin, i.e. , seminomas, relative to normal testis control, nonseminomas, or Leydig tumor cells. (aacrjournals.org)
  • lesions
  • Because different DNA-damaging agents generate different DNA lesions, a key question in damage signaling is how the checkpoint proteins recognize different DNA lesions. (pnas.org)
  • defective
  • When, concurrently, oncologists began examining the mechanisms of oncogenesis in higher eukaryotes using the same molecular biology techniques as their cell cycle counterparts, it was revealed that many cancer cells have defective G 1 checkpoint mechanisms and that cancer cells depend on G 2 checkpoint far more than normal cells ( 4 , 5 ). (aacrjournals.org)
  • The original attempts using caffeine to disrupt the G 2 checkpoint to sensitize G 1 -defective cancer cells were published in 1995 ( 6 , 7 ). (aacrjournals.org)
  • single-stranded
  • In these instances, single-stranded DNA binding proteins are essential for the sequestration and processing of single-stranded DNA. (biomedcentral.com)
  • In order to bind single-stranded DNA, these proteins utilise a characteristic and evolutionary conserved single-stranded DNA-binding domain, the oligonucleotide/oligosaccharide-binding (OB)-fold. (biomedcentral.com)
  • The human genome encodes both simple and higher order SSBs: the simple SSBs are represented by human single-stranded DNA binding proteins 1 and 2 (hSSB1 and 2) and the mitochondrial SSB (mtSSB), while higher order SSBs are represented by heterotrimeric RPA. (biomedcentral.com)
  • Function
  • Many of the oncogenic strains of DNA viruses such as polyomavirus, adenovirus, papillomavirus, and simian sarcoma virus 40 have proteins that impair the function of p53 and RB ( 10 ). (aacrjournals.org)
  • We found that Spy1 can activate cdk2 during the DNA damage response and that expression of a dominant-negative form of cdk2 overrides Spy1 function in damaged cells. (aacrjournals.org)
  • The MMR proteins also function in signaling DNA damage ( 7 , 11 ). (pnas.org)
  • Schematic representation of human OB-fold containing proteins, illustrating their predicted domains and central function. (biomedcentral.com)
  • MMS4 and MUS81 are in the same epistasis group for spore viability, consistent with biochemical data that show that the two proteins function in a complex. (genetics.org)
  • Here we show that the ZMM proteins Msh4 and Msh5 are required for normal chiasma formation, and we propose that they have a pro-CO function outside a canonical class I pathway in Tetrahymena . (genetics.org)
  • activates
  • We also show that cdk2 is required for Spy1-enhanced cell viability and that Spy1 activates cdk2 under conditions of genotoxic stress. (aacrjournals.org)
  • hHUS1
  • Furthermore, overexpression of HHUS1B in human 293 cells causes significant loss of clonogenicity, whereas similar studies with HHUS1 reveal no such effect. (aacrjournals.org)
  • These findings suggested that HHUS1 and HHUS1B have related but not identical functions in cell cycle checkpoint control and perhaps other as of yet undefined cellular processes. (aacrjournals.org)
  • significantly
  • this suppression was not thought to effect any checkpoints because it was presumed that the checkpoint signal cascades were significantly different between bacteria and eukaryotes. (aacrjournals.org)
  • In yeast, 436 proteins were identified, a significantly larger number of hits than were expected by chance. (biomedcentral.com)
  • These SCD-containing proteins did not distribute equally across GO-ontology terms, but were significantly enriched for those involved in processes related to the DDR. (biomedcentral.com)
  • CDC25C
  • Most of the damage signals originated by the sensor complexes for the G 2 checkpoint are conducted to CDC25C, the activity of which is modulated by 14-3-3. (aacrjournals.org)