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  • Mutation
  • Failure of the spindle checkpoint caused by mutation of the responsible genes may be one of the important factors for the development of aneuploidy. (bmj.com)
  • Evidence such as tumour specific aneuploidy, presence of aneuploidy in various preneoplastic conditions, increased frequency of genetic instability in aneuploid cell lines compared with diploid cells, and mutation of mitotic checkpoint genes suggests that aneuploidy possibly plays an active role in carcinogenesis. (bmj.com)
  • It plays an important role in the suppression of proliferation-associated genes, and its gene mutation and increased expression may be associated with human cancer. (cancerindex.org)
  • We recently reported that a synthetic genetic array (SGA) analysis identified genes required for viability when rereplication controls were partially compromised by combining the ORC6-rxl mutation blocking Clb5 binding to Orc6, and the CDC6 Δ NT mutation, an N-terminal truncation resulting in abrogation of Cdk control of Cdc6 activity (see above). (genetics.org)
  • Similarly, inactivation of particular tumor suppressor gene(s) by mutation and deletion may affect key functional pathways and result in different gene expression profiles. (aacrjournals.org)
  • To do this, they deleted each gene one at a time, in combination with another mutation. (technologynetworks.com)
  • The researchers ended up with 172 drug-gene mutation combinations that successfully killed both yeast and human cancer cells. (technologynetworks.com)
  • But this study suggests that this class of drugs should be evaluated for efficacy in any tumor with a mutation that inhibits RAD17, a tumor-suppressor gene that normally helps cells fix damaged DNA. (technologynetworks.com)
  • RAD53
  • Phosphorylation sites that are targeted by Rad53 in mitotic S phase checkpoint responses are also involved, based on the behavior of cells containing mutations in the DBF4 and SLD3 DNA replication genes. (g3journal.org)
  • tumor
  • Some studies show it could inhibit some anti-apoptotic gene and activate some pro-apoptotic gene, its injection solution is one of the new anticancer medicine that can significantly inhibit a various kinds of tumor cells, so it has become the core of research that how to further explore KLT injection to promote tumor cell apoptosis by impacting on related genes. (studyres.com)
  • Accordingly, LOH may indicate regions harboring tumor suppressor genes. (aacrjournals.org)
  • But it's much harder to develop therapies that restore malfunctioning genes that should be triggering cell death in abnormal cells, known as tumor-suppressor genes. (technologynetworks.com)
  • Rather than target a tumor-suppressor gene directly, Ideker and team took the approach of identifying genetic interactions between a tumor suppressor gene and another gene, such that simultaneous disruption of both genes selectively kills cancer cells. (technologynetworks.com)
  • The researchers first used yeast to quickly and cheaply screen 169,000 interactions between yeast versions of human tumor-suppressor genes and genes that can be inhibited with drugs, sometimes called "druggable" targets. (technologynetworks.com)
  • They tested these drugs one at a time for lethal interaction with 112 different tumor-suppressor gene mutations in human cancer cells growing in the lab. (technologynetworks.com)
  • The large chromosomal deletions frequently observed in cancer genomes are often thought to arise as a "two-hit" mechanism in the process of tumor-suppressor gene (TSG) inactivation. (pnas.org)
  • By targeting the mouse orthologs of genes frequently deleted on human 8p22 and adjacent regions, which are lost in approximately half of several other major epithelial cancers, we provide evidence suggesting that multiple genes on chromosome 8p can cooperatively inhibit tumorigenesis in mice, and that their cosuppression can synergistically promote tumor growth. (pnas.org)
  • Early studies on the tumor-suppressor genes (TSGs) RB and TP53 suggested that such deletions can arise as a single mechanism for loss of heterozygosity and, consequently, it is often assumed that they provide a "second-hit" event to inactivate a single TSG ( 1 ). (pnas.org)
  • signaling pathway
  • RNAi-based gene silencing of 53BP1 or NFBD1 has shown impaired phosphorylation of SQ/TQ [ataxia-telangiectasia mutated/ATM and Rad3-related (ATM/ATR) substrates] at IRIF, intra-S, and G 2 -M checkpoints and has thereby revealed essential roles for 53BP1 and NFBD1 in the DNA damage signaling pathway. (aacrjournals.org)
  • downstream
  • The bacteria may target these host factors directly while some induced genes may represent downstream effects due to the presence of the bacteria. (biomedcentral.com)
  • cancers
  • Overexpression of Rad17 has been associated with human breast and colon cancers [ PMID: 10232579 , PMID: 11555598 ]. (ebi.ac.uk)
  • Gene expression array profiles identify subclasses of breast cancers with different clinical outcomes and different molecular features. (aacrjournals.org)
  • LOH) with subclasses of breast cancers having distinct gene expression signatures. (aacrjournals.org)
  • Most cancers have gene mutations that do one of two things - promote cell growth or prevent cell death. (technologynetworks.com)
  • chromatin
  • Rad17 participates in the recruitment of the 9-1-1 complex onto chromatin. (ebi.ac.uk)
  • For representative genes, we illustrate relationships between DNA methylation, the local chromatin state, DNaseI hypersensitivity, and gene expression. (mdpi.com)
  • These studies have demonstrated that relationships between DNA methylation and gene expression are much more complex than previously assumed and often highly dependent on the context of the gene region, the surrounding chromatin epigenetics, and the cell type [ 8 , 9 , 10 ]. (mdpi.com)
  • Furthermore
  • Furthermore, exclusive association between biological subclasses and restricted LOH events provides rationale to search for targeted genes. (aacrjournals.org)
  • recombination
  • Besides checkpoint activation, Rad17 may also serve as a sensor of DNA replication progression, and may be involved in homologous recombination [ PMID: 15297881 ]. (ebi.ac.uk)