Search results for "mutant"
showing 10 items of 670 documents
Bleomycin genotoxicity alteration by glutathione and cytochrome P-450 cellular content in respiratory proficient and deficient strains of Saccharomyc…
1999
The genotoxic effects of the antiblastic drug bleomycin were studied in the D7 strain of Saccharomyces cerevisiae and on its derivative mitochondrial mutant rho degree at different cellular concentrations of two drug metabolizing systems, glutathione (GSH) and cytochrome P-450. Bleomycin mutagenic activity was evaluated as frequencies of mitotic gene conversion, reversion and total aberrations under different physiological conditions. In the D7 strain, petite mutant induction was also detected. This is important due to the role of the mitochondrial genome in cancer induction, ageing and degenerative diseases. Both strains showed higher convertant than revertant induction. At high cytochrome…
DNA binding of L1 is required for human papillomavirus morphogenesis in vivo.
2002
AbstractThe role of putative DNA-binding domains of human papillomavirus (HPV) capsid proteins for DNA encapsidation in vivo is still unknown. We have now analyzed mutants of the major capsid protein L1 of HPV type 33, which are defective for DNA binding, for their ability to encapsidate DNA using an in vivo packaging approach. Since the DNA-binding domain and the nuclear localization signal (NLS) of L1 overlap, both a carboxy-terminal deletion mutant (L1-1/470) and a substitution mutant (L1-1/477M9) were analyzed. L1-1/477M9 has the classical NLS replaced by a noncanonical NLS taken from the human hnRNP protein A1. The mutant proteins were defective for DNA binding in contrast to wild-type…
A genetic approach to dissect the role of prefoldins in Arabidopsis
2021
SummaryThe prefoldin complex (PFDc) was identified in humans as co-chaperone of the cytosolic chaperonin TRiC/CCT. It is conserved in eukaryotes and is composed of subunits PFD1 to 6. PFDc-TRiC/CCT operates folding actin and tubulins. In addition to this function, PFDs participate in a wide range of cellular processes, both in the cytoplasm and in the nucleus, and their malfunction cause developmental alterations and disease in animals, and altered growth and environmental responses in yeast and plants. Genetic analyses in yeast indicate that not all functions performed by PFDs require the participation of the canonical complex. The lack of systematic genetic analyses in higher eukaryotes m…
Cyclin-dependent kinase inhibitor p21 controls adult neural stem cell expansion by regulating Sox2 gene expression.
2012
Summary In the adult brain, continual neurogenesis of olfactory neurons is sustained by the existence of neural stem cells (NSCs) in the subependymal niche. Elimination of the cyclin-dependent kinase inhibitor 1A (p21) leads to premature exhaustion of the subependymal NSC pool, suggesting a relationship between cell cycle control and long-term self-renewal, but the molecular mechanisms underlying NSC maintenance by p21 remain unexplored. Here we identify a function of p21 in the direct regulation of the expression of pluripotency factor Sox2, a key regulator of the specification and maintenance of neural progenitors. We observe that p21 directly binds a Sox2 enhancer and negatively regulate…
EGFP Reporters for Direct and Sensitive Detection of Mutagenic Bypass of DNA Lesions
2020
The sustainment of replication and transcription of damaged DNA is essential for cell survival under genotoxic stress
The high rate of endoreduplication in the repair deficient CHO mutant EM9 parallels a reduced level of methylated deoxycytidine in DNA
2008
It has been recently proposed that hypomethylation of DNA induced by 5-azacytidine (5-azaC) leads to reduced chromatid decatenation that ends up in endoreduplication, most likely due to a failure in topo II function [S. Mateos, I. Domínguez, N. Pastor, G. Cantero, F. Cortés, The DNA demethylating 5-azaC induces endoreduplication in cultured Chinese hamster cells, Mutat. Res. 578 (2005) 33-42]. The Chinese hamster mutant cell line EM9 has a high spontaneous frequency of endoreduplication as compared to its parental line AA8. In order to see if this is related to the degree of DNA methylation, we have investigated the basal levels of both endpoints in AA8 and EM9, as well as the effect of ext…
Metabolic and Functional Genomic Studies Identify Deoxythymidylate Kinase as a target in LKB1 Mutant Lung Cancer
2013
Abstract The LKB1/STK11 tumor suppressor encodes a serine/threonine kinase, which coordinates cell growth, polarity, motility, and metabolism. In non–small cell lung carcinoma, LKB1 is somatically inactivated in 25% to 30% of cases, often concurrently with activating KRAS mutations. Here, we used an integrative approach to define novel therapeutic targets in KRAS-driven LKB1-mutant lung cancers. High-throughput RNA interference screens in lung cancer cell lines from genetically engineered mouse models driven by activated KRAS with or without coincident Lkb1 deletion led to the identification of Dtymk, encoding deoxythymidylate kinase (DTYMK), which catalyzes dTTP biosynthesis, as synthetica…
Putrescine as a signal to modulate the indispensable ABA increase under cold stress.
2009
2 páginas -- PAGS nros. 219-220
Rapid 96-well plates DNA extraction and sequencing procedures to identify genome-wide transposon insertion sites in a difficult to lyse bacterium: La…
2014
International audience; Random transposon mutagenesis followed by adequate screening methods is an unavoidable procedure to characterize genetics of bacterial adaptation to environmental changes. We have recently constructed a mutant library of Lactobacillus casei and we aimed to fully annotate it. However, we have observed that, for L. casei which is a difficult to lyse bacterium, methods used to identify the transposon insertion site in a few mutants (transposon rescue by restriction and recircularization or PCR-based methods) were not transposable for a larger number because they are too time-consuming and sometimes not reliable. Here, we describe a method for large-scale and reliable id…
Growth phase-dependent regulation of nuoA-N expression in Escherichia coli K-12 by the Fis protein: upstream binding sites and bioenergetic significa…
2000
The expression of the nuoA-N operon of Escherichia coli K-12, which encodes the proton-pumping NADH dehydrogenase I is modulated by growth phase-dependent regulation. Under respiratory growth conditions, expression was stimulated in early exponential, and to a lesser extent in late exponential and stationary growth phases. The stimulation in the early exponential growth phase was not observed in fis mutants, which are deficient for the growth phase-responsive regulator Fis. Neither the alternative sigma factor RpoS nor the integration host factor (IHF) are involved in growth phase-dependent regulation of this operon. When incubated with nuo promoter DNA, isolated Fis protein formed three re…