1,721,074 research outputs found
Drosophila cell cycle under arrest: Uncapped telomeres plead guilty
No full textTelomeres are specialized structures that protect chromosome ends from degradation and fusion events. In most organisms, telomeres consist of short, repetitive G-rich sequences added to chromosome ends by a reverse transcriptase with an internal RNA template, called telomerase. Specific DNA-binding protein complexes associate with telomeric sequences preventing chromosome ends from being recognized as DNA double strand breaks (DSBs). Telomeres that lose their cap activate the DNA damage response (DDR) likewise DSBs and, if inappropriately repaired, generate telomeric fusions, which eventually lead to genome instability. In Drosophila there is not telomerase, and telomere length is maintained by transposition of three specialized retroelements. However, fly telomeres are protected by multi protein complexes like their yeast and vertebrate counterparts; these complexes bind chromosome ends in a sequence-independent fashion and are required to prevent checkpoint activation and end-to-end fusion. Uncapped Drosophila telomeres elicit a DDR just as dysfunctional human telomeres. Most interestingly, uncapped Drosophila telomeres also activate the spindle assembly checkpoint (SAC) by recruiting the SAC kinase BubR1. BubR1 accumulations at chromosome ends trigger the SAC that inhibits the metaphase-to-anaphase transition. These findings, reviewed here, highlight an intriguing and unsuspected connection between telomeres and cell cycle regulation, providing a clue to understand human telomere function
Contaminazione di acque superficiali da parte di ceppi batterici antibiotico-resistenti: fonti e metodologie di controllo.
No full textThe validity of TTC-test for dehydrogenase activity of activated sludges in the presence of chemical inhibitors
No full textImpatto ambientale di microrganismi selezionabili in base ai processi di smaltimento dei liquami
No full textDNA damage response, checkpoint activation and dysfunctional telomeres: face to face between mammalian cells and Drosophila.
No full textEukaryotic cells evolved telomeres, specialized nucleoproteic complexes, to protect and replicate chromosome ends. In most organisms, telomeres consist of short, repetitive G-rich sequences added to chromosome ends by a reverse transcriptase with an internal RNA template, called telomerase. Specific DNA-binding protein complexes associate with telomeric sequences allowing cells to distinguish chromosome ends from sites of DNA damage. When telomeres become dysfunctional, either through excessive shortening or due to defects in the proteins that form their structure, they trigger p53/pRb pathways that limits proliferative lifespan and eventually leads to chromosome instability. Drosophila lacks telomerase, telomeres are assembled in a sequence-independent fashion and their length is maintained by transposition of three specialized retroelements. Nevertheless, fly telomeres are maintained by a number of proteins involved in telomere metabolism as in other eukaryotic systems and that are required to prevent checkpoint activation and end-to-end fusion. Uncapped Drosophila telomeres induce a DNA damage response just as dysfunctional human telomeres. Most interestingly, uncapped Drosophila telomeres also activate the spindle assembly checkpoint (SAC) by recruiting the SAC kinase BubR1. Here we review parallelisms and variations between mammalian and Drosophila cells in the crosstalks between telomeres and cell cycle regulation
The Drosophila histone variant H2A.V works in concert with HP1 to promote kinetochore-driven microtubule formation
Full text linkUnlike other organisms that have evolved distinct H2A variants for different functions, Drosophila melanogaster has
just one variant which is capable of filling many roles. This protein, H2A.V, combines the features of the conserved
variants H2A.Z and H2A.X in transcriptional control/heterochromatin assembly and DNA damage response, respectively.
Here we show that mutations in the gene encoding H2A.V affect chromatin compaction and perturb chromosome
segregation in Drosophila mitotic cells. A microtubule (MT) regrowth assay after cold exposure revealed that loss of
H2A.V impairs the formation of kinetochore-driven (k) fibers, which can account for defects in chromosome
segregation. All defects are rescued by a transgene encoding H2A.V that lacks the H2A.X function in the DNA damage
response, suggesting that the H2A.Z (but not H2A.X) functionality of H2A.V is required for chromosome segregation. We
also found that loss of H2A.V weakens HP1 localization, specifically at the pericentric heterochromatin of metaphase
chromosomes. Interestingly, loss of HP1 yielded not only telomeric fusions but also mitotic defects similar to those seen
in H2A.V null mutants, suggesting a role for HP1 in chromosome segregation. We also show that H2A.V precipitates HP1
from larval brain extracts indicating that both proteins are part of the same complex. Moreover, we found that the
overexpression of HP1 rescues chromosome missegregation and defects in the kinetochore-driven k-fiber regrowth of
H2A.V mutants indicating that both phenotypes are influenced by unbalanced levels of HP1. Collectively, our results
suggest that H2A.V and HP1 work in concert to ensure kinetochore-driven MT growth
Effete, an E2 ubiquitin-conjugating enzyme with multiple roles in Drosophila development and chromatin organization
No full textThe Drosophila effete gene encodes an extremely conserved class I E2 ubiquitin-conjugating enzyme. Growing evidence indicates that Eff is involved in many cellular processes including eye development, maintenance of female germline stem cells, and regulation of apoptosis. Eff is also a major component of Drosophila chromatin and it is particularly enriched in chromatin with repressive properties. In addition, Eff is required for telomere protection and to prevent telomere fusion. Consistent with its multiple roles in chromatin maintenance, Eff is also one of the rare factors that modulate both telomere-induced and heterochromatin-induced position effect variegation
Telomere capping and cellular checkpoints: clues from fruit flies
Full text linkIn most organisms, telomeres consist of repetitive G-rich sequences that are elongated by a specific reverse transcriptase, telomerase. A large number of proteins are recruited by these terminal repeats, forming specialized structures that regulate telomerase activity and protect telomeres from degradation and recombination. Drosophila lacks telomerase and telomere length is maintained by transposition of three specialized retrotransposons. In addition, unlike yeast and mammals, Drosophila telomeres are epigenetically determined, sequence-independent structures. However, several proteins required for Drosophila telomere behavior are evolutionarily conserved. These include the Mre11-Rad50-Nbs (MRN) complex and the Ataxia Telangiectasia Mutated (ATM) kinase, which are required to prevent telomeric fusions. In addition, recent studies have provided evidence that Drosophila uncapped telomeres elicit a DNA damage response (DDR) just as dysfunctional yeast and human telomeres. Uncapped Drosophila telomeres also activate the spindle assembly checkpoint (SAC) by recruiting the SAC kinase BubR1. Telomere-induced DDR and SAC both require the wild type function of the MRN complex. In addition, while DDR is mediated by ATR kinase, SAC activation requires both the ATM and ATR activities. These results indicate that the DNA repair systems play multiple roles at Drosophila telomeres, highlighting the importance of this model organism for investigations on the relationships between DNA repair and telomere maintenance
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