Search results for "Cell Cycle"
showing 10 items of 804 documents
ATRIP protects progenitor cells against DNA damage in vivo
2020
AbstractThe maintenance of genomic stability during the cell cycle of progenitor cells is essential for the faithful transmission of genetic information. Mutations in genes that ensure genome stability lead to human developmental syndromes. Mutations in Ataxia Telangiectasia and Rad3-related (ATR) or in ATR-interacting protein (ATRIP) lead to Seckel syndrome, which is characterized by developmental malformations and short life expectancy. While the roles of ATR in replicative stress response and chromosomal segregation are well established, it is unknown how ATRIP contributes to maintaining genomic stability in progenitor cells in vivo. Here, we generated the first mouse model to investigat…
Availability of polyphenols in fruit beverages subjected to in vitro gastrointestinal digestion and their effects on proliferation, cell-cycle and ap…
2009
Abstract Three fruit beverages: Fb (grape–orange–apricot), FbFe (Fb + iron sulphate) and FbFeM (FbFe + skimmed milk) were subjected to in vitro gastrointestinal digestion. Addition of Fe and milk decreased the phenolic content of Fb by 13% and 55%, respectively. The digestion process decreased the phenolic content by 47%, 60%, and 70% in Fb, FbFe and FbFeM with respect to the initial, non-digested, Fb. Caco-2 cells were incubated for 4 h daily for four days or continuously for 24 h with bioaccessible fractions obtained after the digestion (digests). Polyphenols were not metabolised by Caco-2 cells. Fb digest (∼50 μM total phenolics) was the sample that led to the highest inhibition of cell …
In silico, spectroscopic, and biological insights on annelated pyrrolo[3,2-e]pyrimidines with antiproliferative activity
2013
The in silico COMPARE analysis was performed on 8-[3-(piperidino)propyl]-4,10-dimethyl-9-phenyl-6-(methylsulfanyl)-3,4-dihydropyrimido[1,2-c]pyrrolo[3,2-e]pyrimidin-2(8H)-one, a compound with promising antiproliferative activity, previously synthetized and screened against a panel of 60 human tumor cell lines. The results evidenced that this compound matches the biological properties of Chromomycin A3 and Actinomycin D, known drugs with high DNA binding affinity. Prompted by such results, a thorough spectroscopic investigation of its DNA aqueous solutions was performed, with the aim to verify its DNA-binding properties. DNA groove-binding interaction was assigned by UV-vis spectrophotometri…
Hypoxie beim Zervixkarzinom: Pathogenese, Charakterisierung und biologische/klinische Konsequenzen 1
2001
Approximately 60% of locally advanced carcinomas of the uterine cervix exhibit hypoxic and/or anoxic tissue areas which are heterogeneously distributed within the tumor mass. Hypoxia is caused by structural and functional abnormalities of the newly formed tumor vessels arising from neovascularization, by a disturbed microcirculation, enlarged diffusion distances and by tumor- or therapy-associated anemia. The extent of pretherapeutically measured hypoxic tissue areas is independent of clinical size, FIGO stage and histopathological grade of squamous cell carcinomas of the uterine cervix. Anemia can intensify tumor hypoxia. O2-tensions in local recurrences are even lower than those in the pr…
p53 is involved in regulation of the DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT) by DNA damaging agents
1998
The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is inducible by genotoxic stress. MGMT induction results from transcriptional activation of the MGMT gene which is a specific response to DNA damage. A possible factor involved in triggering MGMT induction might be p53, because both p53 and MGMT are activated by DNA breaks. To study the effect of p53 on induction of the MGMT gene, we compared the presence of functional wild-type (wt) and mutant p53 with MGMT expression level in various mouse fibroblasts and rat hepatoma cell lines upon genotoxic treatment. Cells which responded to ionizing radiation (IR) by MGMT induction displayed functional p53, whereas in cells not expr…
Down-regulation of transcription factors AP-1, Sp-1, and NF-kappa B precedes myocyte differentiation.
1996
Terminal differentiation of myocytes involves withdrawal from the cell cycle, induction of myogenin expression, and finally formation of myotubes. To study the factors that regulate the initial phase of muscle differentiation, we analyzed the binding activities of transcription factors AP-1, Sp-1, and NF-kappa B in L6, C2C12, and rhabdomyosarcoma BA-Han-1C cells. Temporal changes in transcription factor binding activities were compared to the activation of myogenin promoter-driven CAT reporter gene and the expression level of myogenin, a master gene of myogenic differentiation. We observed a prominent decrease in the nuclear binding activities of AP-1, Sp-1, and NF-kappa B already 12 to 24 …
TFIIH Operates through an Expanded Proximal Promoter To Fine-Tune c-myc Expression
2004
A continuous stream of activating and repressing signals is processed by the transcription complex paused at the promoter of the c-myc proto-oncogene. The general transcription factor IIH (TFIIH) is held at promoters prior to promoter escape and so is well situated to channel the input of activators and repressors to modulate c-myc expression. We have compared cells expressing only a mutated p89 (xeroderma pigmentosum complementation group B [XPB]), the largest TFIIH subunit, with the same cells functionally complemented with the wild-type protein (XPB/wt-p89). Here, we show structural, compositional, and functional differences in transcription complexes between XPB and XPB/wt-89 cells at t…
Epigenetic Transcriptional Regulation of the Growth Arrest-Specific gene 1 (Gas1) in Hepatic Cell Proliferation at Mononucleosomal Resolution
2011
Background Gas1 (growth arrest-specific 1) gene is known to inhibit cell proliferation in a variety of models, but its possible implication in regulating quiescence in adult tissues has not been examined to date. The knowledge of how Gas1 is regulated in quiescence may contribute to understand the deregulation occurring in neoplastic diseases. Methodology/Principal Findings Gas1 expression has been studied in quiescent murine liver and during the naturally synchronized cell proliferation after partial hepatectomy. Chromatin immunoprecipitation at nucleosomal resolution (Nuc-ChIP) has been used to carry out the study preserving the in vivo conditions. Transcription has been assessed at real …
The nucleosome remodeling factor ISWI functionally interacts with an evolutionarily conserved network of cellular factors
2010
Abstract ISWI is an evolutionarily conserved ATP-dependent chromatin remodeling factor playing central roles in DNA replication, RNA transcription, and chromosome organization. The variety of biological functions dependent on ISWI suggests that its activity could be highly regulated. Our group has previously isolated and characterized new cellular activities that positively regulate ISWI in Drosophila melanogaster. To identify factors that antagonize ISWI activity we developed a novel in vivo eye-based assay to screen for genetic suppressors of ISWI. Our screen revealed that ISWI interacts with an evolutionarily conserved network of cellular and nuclear factors that escaped previous genetic…
DNA adduct levels associated with p53 induction and delay of MCF-7 cells in S phase after exposure to benzo[g]chrysene dihydrodiol epoxide enantiomer…
1998
Optically active isomers of a mammary carcinogen, anti-benzo[g]chrysene 11, 12-dihydrodiol 13, 14-epoxide, react to different extents with DNA and generate DNA adducts that differ in their stereochemistry. In the study reported here, the effect of these two enantiomers on the progress of human breast carcinoma MCF-7 cells through the cell cycle was investigated. Each enantiomer caused the cells to accumulate in the S phase, but a higher dose of the benzo[g]chrysene 11S, 12R-dihydrodiol 13R, 14S-epoxide than of its enantiomer was required to induce this effect. Similarly, induction of p53 also required a higher dose of benzo[g]chrysene 11S, 12R-dihydrodiol 13R, 14S-epoxide. Postlabeling stud…