D-loop
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Homologous recombination involves the formation of branched DNA molecules that may interfere with chromosome segregation. To resolve these persistent joint molecules, cells rely on the activation of structure-selective endonucleases (SSEs) during the late stages of the cell cycle. However, the premature activation of SSEs compromises genome integrity, due to untimely processing of replication and/or recombination intermediates. Here, we used a biochemical approach to show that the budding yeast SSEs Mus81 and Yen1 possess the ability to cleave the central recombination intermediate known as the displacement loop or D-loop. Moreover, we demonstrate that, consistently with previous genetic data, the simultaneous action of Mus81 and Yen1, followed by ligation, is sufficient to recreate the formation of a half-crossover precursor in vitro. Our results provide not only mechanistic explanation for the formation of a half-crossover, but also highlight the critical importance for precise regulation of these SSEs to prevent chromosomal rearrangements.
- MeSH
- crossing over (genetika) * MeSH
- DNA vazebné proteiny * metabolismus genetika MeSH
- endonukleasy * metabolismus genetika MeSH
- homologní rekombinace MeSH
- resolvasy Hollidayova spoje metabolismus genetika MeSH
- Saccharomyces cerevisiae - proteiny * metabolismus genetika MeSH
- Saccharomyces cerevisiae genetika metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
Homologous recombination (HR) is essential for maintaining genomic integrity, which is challenged by a wide variety of potentially lethal DNA lesions. Regardless of the damage type, recombination is known to proceed by RAD51-mediated D-loop formation, followed by DNA repair synthesis. Nevertheless, the participating polymerases and extension mechanism are not well characterized. Here, we present a reconstitution of this step using purified human proteins. In addition to Pol δ, TLS polymerases, including Pol η and Pol κ, also can extend D-loops. In vivo characterization reveals that Pol η and Pol κ are involved in redundant pathways for HR. In addition, the presence of PCNA on the D-loop regulates the length of the extension tracks by recruiting various polymerases and might present a regulatory point for the various recombination outcomes.
- MeSH
- DNA-dependentní DNA-polymerasy chemie fyziologie MeSH
- DNA-polymerasa III chemie fyziologie MeSH
- HeLa buňky MeSH
- homologní rekombinace * MeSH
- jednovláknová DNA biosyntéza MeSH
- lidé MeSH
- osmolární koncentrace MeSH
- poškození DNA MeSH
- proliferační antigen buněčného jádra chemie fyziologie MeSH
- protein FUS vázající RNA chemie fyziologie MeSH
- rekombinasa Rad51 chemie MeSH
- replikace DNA MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Telomeric repeat binding factor 2 (TRF2) folds human telomeres into loops to prevent unwanted DNA repair and chromosome end-joining. The N-terminal basic domain of TRF2 (B-domain) protects the telomeric displacement loop (D-loop) from cleavage by endonucleases. Repressor activator protein 1 (Rap1) binds TRF2 and improves telomeric DNA recognition. We found that the B-domain of TRF2 stabilized the D-loop and thus reduced unwinding by BLM and RPA, whereas the formation of the Rap1-TRF2 complex restored DNA unwinding. To understand how the B-domain of TRF2 affects DNA binding and D-loop processing, we analyzed DNA binding of full-length TRF2 and a truncated TRF2 construct lacking the B-domain. We quantified how the B-domain improves TRF2's interaction with DNA via enhanced long-range electrostatic interactions. We developed a structural envelope model of the B-domain bound on DNA. The model revealed that the B-domain is flexible in solution but becomes rigid upon binding to telomeric DNA. We proposed a mechanism for how the B-domain stabilizes the D-loop.
In order to assess the DNA sequence variation and phylogenetic relationship among five tuna species (Auxis thazard, Euthynnus affinis, Katsuwonus pelamis, Thunnus tonggol, and T. albacares) out of all four tuna genera, partial sequences of the mitochondrial DNA (mtDNA) D-loop region were analyzed. The estimate of intra-specific sequence variation in studied species was low, ranging from 0.027 to 0.080 [Kimura's two parameter distance (K2P)], whereas values of inter-specific variation ranged from 0.049 to 0.491. The longtail tuna (T. tonggol) and yellowfin tuna (T. albacares) were found to share a close relationship (K2P = 0.049) while skipjack tuna (K. pelamis) was most divergent studied species. Phylogenetic analysis using Maximum-Likelihood (ML) and Neighbor-Joining (NJ) methods supported the monophyletic origin of Thunnus species. Similarly, phylogeny of Auxis and Euthynnus species substantiate the monophyly. However, results showed a distinct origin of K. pelamis from genus Thunnus as well as Auxis and Euthynnus. Thus, the mtDNA D-loop region sequence data supports the polyphyletic origin of tuna species.
- MeSH
- fylogeneze * MeSH
- genetická variace * MeSH
- konformace nukleové kyseliny * MeSH
- mitochondriální DNA chemie genetika MeSH
- pravděpodobnostní funkce MeSH
- sekvence nukleotidů MeSH
- sekvenční analýza DNA metody MeSH
- tuňák genetika MeSH
- zeměpis MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Abasic (AP) lesions are the most frequent type of damages occurring in cellular DNA. Here we describe the conformational effects of AP sites substituted for 2'-deoxyadenosine in the first (ap7), second (ap13) or third (ap19) loop of the quadruplex formed in K(+) by the human telomere DNA 5'-d[AG3(TTAG3)3]. CD spectra and electrophoresis reveal that the presence of AP sites does not hinder the formation of intramolecular quadruplexes. NMR spectra show that the structural heterogeneity is substantially reduced in ap7 and ap19 as compared to that in the wild-type. These two (ap7 and ap19) sequences are shown to adopt the hybrid-1 and hybrid-2 quadruplex topology, respectively, with AP site located in a propeller-like loop. All three studied sequences transform easily into parallel quadruplex in dehydrating ethanol solution. Thus, the AP site in any loop region facilitates the formation of the propeller loop. Substitution of all adenines by AP sites stabilizes the parallel quadruplex even in the absence of ethanol. Whereas guanines are the major determinants of quadruplex stability, the presence or absence of loop adenines substantially influences quadruplex folding. The naturally occurring adenine-lacking sites in the human telomere DNA can change the quadruplex topology in vivo with potentially vital biological consequences.
European heart journal ; Vol. 10 Suppl. H/1989
116 s. : obr., tab., bibliogr.
The objective of this study was to provide deeper knowledge of the maternal genetic structure and demographic history of the human populations of the Sahel/Savannah belt, the extensive region lying between the Sahara and tropical rainforests, spanning from the Atlantic Ocean to the Red Sea coast. The study aimed to confirm or disconfirm archaeological and linguistic data indicating that the region's populations underwent diversification as a result of the spread of agropastoral food-producing subsistence lifestyles, over time dividing the region into separate areas of nomadic pastoralism, on the one hand, and sedentary farming, on the other. To perform both descriptive and coalescence analyses from the Sahel/Savannah belt's entire region, including western and eastern rather than just central populations studied previously, we generated a new mitochondrial DNA (mtDNA) data set not only having almost 2,000 samples (875 of which were newly collected) but also encompassing whole mtDNA D-loop segment rather than only the previously studied hypervariable segment 1. While comparing our analyses with previous results from the Lake Chad Basin (central Sahel/Savannah Belt), we found similar intrapopulation diversity measures (i.e., lower values in pastoralists than in farmers). However, the new data set pointed to significant differences in mating strategies between western and eastern pastoralists: our results suggest higher gene flow between the Arabic pastoralists and neighboring farmers in the eastern part than between the Fulani pastoralists and their sedentary neighbors in the western part of the Sahel/Savannah belt. The findings are discussed in light of archaeological and linguistic data, allowing us to postulate that the genetic differentiation of Fulani pastoralists from the common western African agropastoral gene pool occurred at around the same time as the arrival of the Arabic pastoralists to eastern Africa. However, it seems that while the process of divergence of the Fulani pastoralists in the west was accompanied by a loss of Fulani females to other populations, the Arab pastoralists' immigration to the Sahel/Savannah belt conversely resulted in some gain of local females into this Arab population.
- MeSH
- Arabové genetika MeSH
- archeologie metody MeSH
- černoši genetika dějiny MeSH
- dějiny starověku MeSH
- dějiny středověku MeSH
- emigrace a imigrace MeSH
- genetické struktury MeSH
- jazyk (prostředek komunikace) MeSH
- jednonukleotidový polymorfismus genetika MeSH
- lidé MeSH
- mitochondriální DNA genetika MeSH
- osoby s přechodným pobytem a migranti MeSH
- populační genetika MeSH
- tok genů genetika MeSH
- zemědělství trendy MeSH
- Check Tag
- dějiny starověku MeSH
- dějiny středověku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- historické články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Geografické názvy
- severní Afrika MeSH
- MeSH
- dechové testy MeSH
- dyspepsie MeSH
- glukosa MeSH
- lidé MeSH
- rifaximin terapeutické užití MeSH
- syndrom slepé kličky * diagnóza MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Článek shrnuje problematiku jednoho z nejběžnějších syndromů v gastroenterologické praxi, laktózové intolerance, z pohledu alergologa a imunologa: genetiku persistence laktázové aktivity, rozvoj symptomů laktózové intolerance, diagnostiku této poruchy a její řešení (dietní opatření, popřípadě medikamentózní léčbu). Pozornost je věnována vztahu k dalším potravinovým reakcím a jiným onemocněním.
This review discusses one of the most common problems in gastrointestinal clinical practice, lactose intolerance, from the poin t of view of allergy and immunology: the role of lactase-persistence alleles, the development of lactose intolerance symptoms, diagnosis of this problem and its management (alimentary restriction and drug therapy). Special attention is given to understanding connections with anot her alimentary reactions and another diseases.
- MeSH
- alergie na mléko diagnóza patofyziologie MeSH
- dietoterapie MeSH
- diferenciální diagnóza MeSH
- laktasa genetika nedostatek terapeutické užití MeSH
- laktosa fyziologie metabolismus MeSH
- lidé MeSH
- nesnášenlivost laktózy * diagnóza etiologie patofyziologie terapie MeSH
- potravní doplňky MeSH
- probiotika terapeutické užití MeSH
- syndrom slepé kličky diagnóza patofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
