Search results for "PAI"

DNA Injury and Repair Systems

2018

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The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress

2015

The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful DNA replication and preventing replication stress is also emerging. Inactivation of the MRN complex invariably leads to developmental and/or degenerative neuronal defects, the pathogenesis of which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly and strongly impaired cerebellar development, both in humans and in the mouse model. These phenotypes strikingly overlap those induced by inactivation of MYCN, an essential promoter of the expansion of neuronal stem and progenitor cells, suggesting that MYCN and the MRN complex migh…

DNA-BINDING and DNA-protecting activities of small natural organic molecules and food extracts

2020

The review summarizes literature data on the DNA-binding, DNA-protecting and DNA-damaging activities of a range of natural human endogenous and exogenous compounds. Small natural organic molecules bind DNA in a site-specific mode, by arranging tight touch with the structure of the major and minor grooves, as well as individual bases in the local duplex DNA. Polyphenols are the best-studied exogenous compounds from this point of view. Many of them demonstrate hormetic effects, producing both beneficial and damaging effects. An attempt to establish the dependence of DNA damage or DNA protection on the concentration of the compound turned out to be successful for some polyphenols, daidzein, ge…

Inherent and toxicant-provoked reduction in DNA repair capacity: A key mechanism for personalized risk assessment, cancer prevention and intervention…

2018

Abstract Genomic investigations reveal novel evidence which indicates that genetic predisposition and inherent drug response are key factors for development of cancer and for poor response to therapy. However, mechanisms for these outcomes and interactions with environmental factors have not been well-characterized. Therefore, cancer risk, prevention, intervention and prognosis determinations have still mainly been based on population, rather than on individualized, evaluations. The objective of this review was to demonstrate that a key mechanism which contributes to the determination is inherent and/or toxicant-provoked reduction in DNA repair capacity. In addition, functional and quantita…

2016

DNA damage can significantly modulate expression of the affected genes either by direct structural interference with transcription components or as a collateral outcome of cellular repair attempts. Thus, DNA glycosylases of the base excision repair (BER) pathway have been implicated in negative transcriptional response to several spontaneously generated DNA base modifications, including a common oxidative DNA base modification 8-oxoguanine (8-oxoG). Here, we report that single 8-oxoG situated in the non-transcribed DNA strand of a reporter gene has a pronounced negative effect on transcription, driven by promoters of various strength and with different structural properties, including viral…

Photobacterium malacitanum sp. nov., and Photobacterium andalusiense sp. nov., two new bacteria isolated from diseased farmed fish in Southern Spain.

2018

Three strains, H01100409BT, H01100413B, and H27100402HT, were isolated from several internal organs of diseased redbanded seabream (Pagrus auriga) reared in Andalusia (Southern Spain). All strains were studied by phenotypic, including chemotaxonomy, and genomic characteristics. Phylogenetic analysis based on concatenated sequences of six housekeeping genes (gyrB, ftsZ, topA, mreB, gapA, and 16S rRNA) supported the inclusion of the strains within the clade Phosphoreum of the genus Photobacterium, and two of the strains (H27100402HT and H01100409BT) formed a tight group separated from the closest species P. aquimaris. Genomic analyses, including average nucleotide identity (ANIb and ANIm) and…

Photobacterium toruni sp. nov., a bacterium isolated from diseased farmed fish.

2017

Three bacterial strains were isolated from liver and spleen of diseased farmed redbanded seabream (Pagrus auriga) in south-west Spain. Their partial 16S rRNA gene sequences clustered within those of the genus Photobacterium , showing high similarity (98.6–99.3 %) to the type strains of Photobacterium iliopiscarium , P. piscicola , P. kishitanii , P. aquimaris and P. phosphoreum . Multilocus sequence analysis using six housekeeping genes (gapA, topA, mreB, ftsZ, gyrB and 16S rRNA) confirmed the new strains as forming an independent branch with a bootstrap value of 100, likely to represent a novel species. To confirm this, we used whole genome sequencing and genomic analysis (ANIb, ANIm and i…

Ruegeria denitrificans sp. nov., a marine bacterium in the family Rhodobacteraceae with the potential ability for cyanophycin synthesis.

2018

Strain CECT 5091T, an aerobic, marine, Gram-reaction- and Gram-stain-negative, chemoheterotrophic bacterium was isolated from oysters harvested off the Spanish Mediterranean coast. Analysis of the 16S rRNA gene sequence placed the strain within the genus Ruegeria , in the family Rhodobacteraceae , with 16S rRNA gene similarities of 98.7, 98.7 and 98.4 % to Ruegeria conchae , Ruegeria atlantica and Ruegeria arenilitoris , respectively. Average nucleotide identities (ANI) and in silico DNA–DNA hybridization (DDH) were determined, comparing the genome sequence of CECT 5091T with those of the type strains of 12 species of the genus Ruegeria : the values obtained were always below the thresholds…

Marinomonas spartinae sp. nov., a novel species with plant-beneficial properties.

2016

Two strains of Gram-stain-negative, chemo-organotrophic, aerobic and halophilic gammaproteobacteria, isolated from within the stem and roots of Spartina maritima in salt marshes from the south Atlantic Spanish coast, were found to represent a novel species in the genus Marinomonas through phylogenetic analysis of their 16S rRNA genes and phenotypic characterization. 16S rRNA gene sequences of the two strains shared < 96.2 % similarity with other Marinomonas species, with Marimonas alcarazii being the most similar in sequence. They required sodium ions for growth, were able to thrive at low (4 °C) temperatures and at salinities of 12–15 %, were unable to hydrolyse any tested macromolecule ex…

Contribution of allelic imbalance to colorectal cancer

2018

Point mutations in cancer have been extensively studied but chromosomal gains and losses have been more challenging to interpret due to their unspecific nature. Here we examine high-resolution allelic imbalance (AI) landscape in 1699 colorectal cancers, 256 of which have been whole-genome sequenced (WGSed). The imbalances pinpoint 38 genes as plausible AI targets based on previous knowledge. Unbiased CRISPR-Cas9 knockout and activation screens identified in total 79 genes within AI peaks regulating cell growth. Genetic and functional data implicate loss of TP53 as a sufficient driver of AI. The WGS highlights an influence of copy number aberrations on the rate of detected somatic point muta…