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  • 1
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    The fission yeast FANCM ortholog directs non-crossover recombination during meiosis (2012)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2012-06-23
    Description: The formation of healthy gametes depends on programmed DNA double-strand breaks (DSBs), which are each repaired as a crossover (CO) or non-crossover (NCO) from a homologous template. Although most of these DSBs are repaired without giving COs, little is known about the genetic requirements of NCO-specific recombination. We show that Fml1, the Fanconi anemia complementation group M (FANCM)-ortholog of Schizosaccharomyces pombe, directs the formation of NCOs during meiosis in competition with the Mus81-dependent pro-CO pathway. We also define the Rad51/Dmc1-mediator Swi5-Sfr1 as a major determinant in biasing the recombination process in favor of Mus81, to ensure the appropriate amount of COs to guide meiotic chromosome segregation. The conservation of these proteins from yeast to humans suggests that this interplay may be a general feature of meiotic recombination.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399777/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399777/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lorenz, Alexander -- Osman, Fekret -- Sun, Weili -- Nandi, Saikat -- Steinacher, Roland -- Whitby, Matthew C -- 090767/Wellcome Trust/United Kingdom -- 090767/Z/09/Z/Wellcome Trust/United Kingdom -- J 2489/Austrian Science Fund FWF/Austria -- New York, N.Y. -- Science. 2012 Jun 22;336(6088):1585-8. doi: 10.1126/science.1220111.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Oxford, Oxford, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22723423" target="_blank"〉PubMed〈/a〉
    Keywords: Chromosome Segregation ; Chromosomes, Fungal/physiology ; *Crossing Over, Genetic ; DNA Breaks, Double-Stranded ; DNA Helicases/genetics/*metabolism ; DNA Repair ; DNA, Fungal/chemistry/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Endonucleases/genetics/metabolism ; *Homologous Recombination ; *Meiosis ; Mutation ; Recombinases/genetics/metabolism ; Schizosaccharomyces/*genetics/physiology ; Schizosaccharomyces pombe Proteins/genetics/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
    Electronic Resource
    Electronic Resource
    The Holliday junction resolvase SpCCE1 prevents mitochondrial DNA aggregation in Schizosaccharomyces pombe (2000)
    Springer
    Molecular genetics and genomics 263 (2000), S. 889-897 
    Details
    ISSN: 1617-4623
    Keywords: Key words DNA repair ; Endonuclease ; Holliday junction ; Mitochondria ; Recombination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract SpCCE1 (YDC2) from Schizosaccharomyces pombe is a DNA structure-specific endonuclease that resolves Holliday junctions in vitro. To investigate the in vivo function of SpCCE1 we made an Spcce1::ura4 + insertion mutant strain. This strain is viable and, despite being devoid of the Holliday junction resolvase activity that is readily detected in fractionated extracts from wild-type cells, exhibits normal levels of UV sensitivity and spontaneous or UV-induced mitotic recombination. In accordance with the absence of a nuclear phenotype, we show by fluorescence microscopy that a SpCCE1-GFP fusion localises exclusively to the mitochondria of S. pombe. In Saccharomyces cerevisiae the homologue of SpCCE1, CCE1, is known to function in the mitochondria where its role appears to be to remove recombination junctions and thus facilitate mitochondrial DNA segregation. A similar function can probably be attributed to SpCCE1 in S. pombe, since the majority of mitochondrial DNA from the Spcce1::ura4 + strain is in an aggregated form apparently due to extensive interlinking of DNA molecules by recombination junctions. Surprisingly, this marked effect on the conformation of mitochondrial DNA results in little or no effect on proliferation or viability of the Spcce1::ura4 + strain. Possible explanations are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004380000256
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  • 3
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    Rad51/Dmc1 paralogs and mediators oppose DNA helicases to limit hybrid DNA formation and promote crossovers during meiotic recombination (2014)
    Oxford University Press
    Details
    Publication Date: 2014-12-17
    Description: During meiosis programmed DNA double-strand breaks (DSBs) are repaired by homologous recombination using the sister chromatid or the homologous chromosome (homolog) as a template. This repair results in crossover (CO) and non-crossover (NCO) recombinants. Only CO formation between homologs provides the physical linkages guiding correct chromosome segregation, which are essential to produce healthy gametes. The factors that determine the CO/NCO decision are still poorly understood. Using Schizosaccharomyces pombe as a model we show that the Rad51/Dmc1-paralog complexes Rad55-Rad57 and Rdl1-Rlp1-Sws1 together with Swi5-Sfr1 play a major role in antagonizing both the FANCM-family DNA helicase/translocase Fml1 and the RecQ-type DNA helicase Rqh1 to limit hybrid DNA formation and promote Mus81-Eme1-dependent COs. A common attribute of these protein complexes is an ability to stabilize the Rad51/Dmc1 nucleoprotein filament, and we propose that it is this property that imposes constraints on which enzymes gain access to the recombination intermediate, thereby controlling the manner in which it is processed and resolved.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 4
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    The ATPase activity of Fml1 is essential for its roles in homologous recombination and DNA repair (2012)
    Oxford University Press
    Details
    Publication Date: 2012-10-24
    Description: In fission yeast, the DNA helicase Fml1, which is an orthologue of human FANCM, is a key component of the machinery that drives and governs homologous recombination (HR). During the repair of DNA double-strand breaks by HR, it limits the occurrence of potentially deleterious crossover recombinants, whereas at stalled replication forks, it promotes HR to aid their recovery. Here, we have mutated conserved residues in Fml1’s Walker A (K99R) and Walker B (D196N) motifs to determine whether its activities are dependent on its ability to hydrolyse ATP. Both Fml1 K99R and Fml1 D196N are proficient for DNA binding but totally deficient in DNA unwinding and ATP hydrolysis. In vivo both mutants exhibit a similar reduction in recombination at blocked replication forks as a fml1 mutant indicating that Fml1’s motor activity, fuelled by ATP hydrolysis, is essential for its pro-recombinogenic role. Intriguingly, both fml1 K99R and fml1 D196N mutants exhibit greater sensitivity to genotoxins and higher levels of crossing over during DSB repair than a fml1 strain. These data suggest that without its motor activity, the binding of Fml1 to its DNA substrate can impede alternative mechanisms of repair and crossover avoidance.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 5
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    Rural Resource Development: An Economic Approach (1980)
    Wiley
    Details
    Publication Date: 1980-11-01
    Print ISSN: 0016-7398
    Electronic ISSN: 1475-4959
    Topics: Geography
    Published by Wiley
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