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Journal of the American Academy of Dermatology, ISSN 0190-9622 vol. 43, no. 1, part 2, suppl., July 2000
2A, S30 s. : il., tab. ; 28 cm
F1 hybrids between mouse inbred strains PWD and C57BL/6 represent the most thoroughly genetically defined model of hybrid sterility in vertebrates. Hybrid male sterility can be fully reconstituted from three components of this model, the Prdm9 gene, intersubspecific homeology of Mus musculus musculus and Mus musculus domesticus autosomes, and the X-linked Hstx2 locus. Hstx2 modulates the extent of Prdm9-dependent meiotic arrest and harbors two additional factors responsible for intersubspecific introgression-induced oligospermia (Hstx1) and meiotic recombination rate (Meir1). To facilitate positional cloning and to overcome the recombination suppression within the 4.3 Mb encompassing the Hstx2 locus, we designed Hstx2-CRISPR and SPO11/Cas9 transgenes aimed to induce DNA double-strand breaks specifically within the Hstx2 locus. The resulting recombinant reduced the Hstx2 locus to 2.70 Mb (chromosome X: 66.51-69.21 Mb). The newly defined Hstx2 locus still operates as the major X-linked factor of the F1 hybrid sterility, and controls meiotic chromosome synapsis and meiotic recombination rate. Despite extensive further crosses, the 2.70 Mb Hstx2 interval behaved as a recombination cold spot with reduced PRDM9-mediated H3K4me3 hotspots and absence of DMC1-defined DNA double-strand-break hotspots. To search for structural anomalies as a possible cause of recombination suppression, we used optical mapping and observed high incidence of subspecies-specific structural variants along the X chromosome, with a striking copy number polymorphism of the microRNA Mir465 cluster. This observation together with the absence of a strong sterility phenotype in Fmr1 neighbor (Fmr1nb) null mutants support the role of microRNA as a likely candidate for Hstx2.
- MeSH
- chromozom X genetika MeSH
- histonlysin-N-methyltransferasa genetika MeSH
- homologní rekombinace MeSH
- meióza MeSH
- mikro RNA genetika MeSH
- modifikátorové geny * MeSH
- mužská infertilita genetika MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- polymorfismus genetický * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Srs2 plays many roles in DNA repair, the proper regulation and coordination of which is essential. Post-translational modification by small ubiquitin-like modifier (SUMO) is one such possible mechanism. Here, we investigate the role of SUMO in Srs2 regulation and show that the SUMO-interacting motif (SIM) of Srs2 is important for the interaction with several recombination factors. Lack of SIM, but not proliferating cell nuclear antigen (PCNA)-interacting motif (PIM), leads to increased cell death under circumstances requiring homologous recombination for DNA repair. Simultaneous mutation of SIM in asrs2ΔPIMstrain leads to a decrease in recombination, indicating a pro-recombination role of SUMO. Thus SIM has an ambivalent function in Srs2 regulation; it not only mediates interaction with SUMO-PCNA to promote the anti-recombination function but it also plays a PCNA-independent pro-recombination role, probably by stimulating the formation of recombination complexes. The fact that deletion of PIM suppresses the phenotypes of Srs2 lacking SIM suggests that proper balance between the anti-recombination PCNA-bound and pro-recombination pools of Srs2 is crucial. Notably, sumoylation of Srs2 itself specifically stimulates recombination at the rDNA locus.
- MeSH
- aminokyselinové motivy MeSH
- DNA fungální genetika metabolismus MeSH
- DNA-helikasy genetika metabolismus MeSH
- oprava DNA fyziologie MeSH
- proliferační antigen buněčného jádra genetika metabolismus MeSH
- protein SUMO-1 genetika metabolismus MeSH
- rekombinace genetická fyziologie MeSH
- ribozomální DNA genetika metabolismus MeSH
- Saccharomyces cerevisiae - proteiny genetika metabolismus MeSH
- sumoylace fyziologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Journal of obstetrics and gynaecology, ISSN 0144-3615 vol. 18, suppl. 2, September 1998
71-83 s. : il., tab. ; 30 cm
- MeSH
- adjuvancia imunologická MeSH
- bradavice terapie MeSH
- imunologické faktory MeSH
- infekce papilomavirem imunologie MeSH
- nemoci vulvy epidemiologie MeSH
- Publikační typ
- sborníky MeSH
- Konspekt
- Gynekologie. Porodnictví
- NLK Obory
- gynekologie a porodnictví
- infekční lékařství
The etiology and mechanisms of autism and autism spectrum disorder (ASD) are not yet fully understood. There is currently no treatment for ASD for providing significant improvement in core symptoms. Recent studies suggest, however, that ASD is associated with gut dysbiosis, indicating that modulation of gut microbiota in children with ASD may thus reduce the manifestation of ASD symptoms. The aim of this pilot study (prospective randomized, double-blinded, placebo-controlled) was to evaluate efficacy of the biological response modifier Juvenil in modulating the microbiome of children with ASD and, in particular, whether Juvenil is able to alleviate the symptoms of ASD. In total, 20 children with ASD and 12 neurotypical children were included in our study. Supplementation of ASD children lasted for three months. To confirm Juvenil's impact on the gut microbiome, stool samples were collected from all children and the microbiome's composition was analyzed. This pilot study demonstrated that the gut microbiome of ASD children differed significantly from that of healthy controls and was converted by Juvenil supplementation toward a more neurotypical microbiome that positively modulated children's autism symptoms.
- MeSH
- autistická porucha mikrobiologie MeSH
- dítě MeSH
- dvojitá slepá metoda MeSH
- dysbióza mikrobiologie MeSH
- feces mikrobiologie MeSH
- lidé MeSH
- pilotní projekty MeSH
- poruchy autistického spektra * mikrobiologie MeSH
- potravní doplňky * MeSH
- předškolní dítě MeSH
- prospektivní studie MeSH
- střevní mikroflóra * MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
Small ubiquitin-related modifier-2/3 (SUMO-2/3) is a member of the ubiquitin-like (Ubl) protein family. Conjugation of SUMO-2/3 to target proteins is influenced by various stress conditions and chemical inhibitors. SUMO-2/3 conjugation may serve as a neuroprotective mechanism and may play a role in protein quality control. A method for screening global changes in SUMO-2/3 conjugation would facilitate further research of SUMO-2/3 cellular function. Here we show that dot blot with immunochemical detection allows evaluation of changes in global cellular SUMO-2/3 conjugation and offers an alternative to more laborious Western blot analysis. The method is based on a change of SUMO-2/3 signal intensity upon its conjugation. The dot blot analysis presented here is a time-saving method that enables screening of large numbers of samples and easy statistical evaluation of the results.
- MeSH
- HEK293 buňky MeSH
- imunoblotting metody MeSH
- lidé MeSH
- malé modifikační proteiny související s ubikvitinem * analýza chemie metabolismus MeSH
- ubikvitiny * analýza chemie metabolismus MeSH
- western blotting MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
S. 201-214 : il., tab. ; 24 cm
- MeSH
- inzulin krev MeSH
- krevní proteiny chemie MeSH
- Publikační typ
- vysokoškolské kvalifikační práce MeSH
- Konspekt
- Biochemie. Molekulární biologie. Biofyzika
- NLK Obory
- biochemie
x, 404 s. : il.
In vitro analysis of posttranslational modifications such as sumoylation provides a great tool to not only identify the target proteins but also to characterize the specific effects of this modification on the protein features and uncover possible regulatory mechanism. In this chapter, we will describe the purification of yeast SUMO machinery proteins and their use to identify SUMO modification of target proteins in vitro. Furthermore, we will show several examples characterizing the effect of sumoylation on the biochemical activities of various proteins involved in homologous recombination (HR) that helped to better understand the regulatory role of this modification.
- MeSH
- Escherichia coli genetika růst a vývoj metabolismus MeSH
- homologní rekombinace * MeSH
- komplexy ubikvitinligas metabolismus MeSH
- malé modifikační proteiny související s ubikvitinem metabolismus MeSH
- proteiny z Escherichia coli metabolismus MeSH
- rekombinantní proteiny izolace a purifikace MeSH
- sumoylace MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
