排序方式: 共有63条查询结果,搜索用时 750 毫秒
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Recombination is believed to assist replication when forks collapse. By using an elegant system, Lambert et al. (2005) address the consequences of recombination at blocked forks. They show that chromosomal rearrangements are the price to pay for cell viability when forks collapse. 相似文献
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Background
The availability of interaction databases provides an opportunity for researchers to utilize immense amounts of data exclusively in silico. Recently there has been an emphasis on studying the global properties of biological interactions using network analysis. While this type of analysis offers a wide variety of global insights it has surprisingly not been used to examine more localized interactions based on mechanism. In as such we have particular interest in the role of key topological components in signal transduction cascades as they are vital regulators of healthy and diseased cell states. 相似文献43.
A likelihood method for the detection of selection and recombination using nucleotide sequences 总被引:28,自引:12,他引:16
Different regions along nucleotide sequences are often subject to different
evolutionary forces. Recombination will result in regions having different
evolutionary histories, while selection can cause regions to evolve at
different rates. This paper presents a statistical method based on
likelihood for detecting such processes by identifying the regions which do
not fit with a single phylogenetic topology and nucleotide substitution
process along the entire sequence. Subsequent reanalysis of these anomalous
regions may then be possible. The method is tested using simulations, and
its application is demonstrated using the primate psi eta-globin
pseudogene, the V3 region of the envelope gene of HIV-1, and argF sequences
from Neisseria bacteria. Reanalysis of anomalous regions is shown to reveal
possible immune selection in HIV-1 and recombination in Neisseria. A
computer program which implements the method is available.
相似文献
44.
Diego Dibitetto Matteo Ferrari Chetan C. Rawal Attila Balint TaeHyung Kim Zhaolei Zhang Marcus B. Smolka Grant W. Brown Federica Marini Achille Pellicioli 《Nucleic acids research》2016,44(2):669-682
The DNA damage checkpoint pathway is activated in response to DNA lesions and replication stress to preserve genome integrity. However, hyper-activation of this surveillance system is detrimental to the cell, because it might prevent cell cycle re-start after repair, which may also lead to senescence. Here we show that the scaffold proteins Slx4 and Rtt107 limit checkpoint signalling at a persistent double-strand DNA break (DSB) and at uncapped telomeres. We found that Slx4 is recruited within a few kilobases of an irreparable DSB, through the interaction with Rtt107 and the multi-BRCT domain scaffold Dpb11. In the absence of Slx4 or Rtt107, Rad9 binding near the irreparable DSB is increased, leading to robust checkpoint signalling and slower nucleolytic degradation of the 5′ strand. Importantly, in slx4Δ sae2Δ double mutant cells these phenotypes are exacerbated, causing a severe Rad9-dependent defect in DSB repair. Our study sheds new light on the molecular mechanism that coordinates the processing and repair of DSBs with DNA damage checkpoint signalling, preserving genome integrity. 相似文献
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Nicolas C. Hoch Eric S.-W. Chen Robert Buckland Shun-Chung Wang Alessandro Fazio Andrew Hammet Achille Pellicioli Andrei Chabes Ming-Daw Tsai J?rg Heierhorst 《Molecular and cellular biology》2013,33(16):3202-3213
The essential yeast kinases Mec1 and Rad53, or human ATR and Chk1, are crucial for checkpoint responses to exogenous genotoxic agents, but why they are also required for DNA replication in unperturbed cells remains poorly understood. Here we report that even in the absence of DNA-damaging agents, the rad53-4AQ mutant, lacking the N-terminal Mec1 phosphorylation site cluster, is synthetic lethal with a deletion of the RAD9 DNA damage checkpoint adaptor. This phenotype is caused by an inability of rad53-4AQ to activate the downstream kinase Dun1, which then leads to reduced basal deoxynucleoside triphosphate (dNTP) levels, spontaneous replication fork stalling, and constitutive activation of and dependence on S phase DNA damage checkpoints. Surprisingly, the kinase-deficient rad53-K227A mutant does not share these phenotypes but is rendered inviable by additional phosphosite mutations that prevent its binding to Dun1. The results demonstrate that ultralow Rad53 catalytic activity is sufficient for normal replication of undamaged chromosomes as long as it is targeted toward activation of the effector kinase Dun1. Our findings indicate that the essential S phase function of Rad53 is comprised by the combination of its role in regulating basal dNTP levels and its compensatory kinase function if dNTP levels are perturbed. 相似文献
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Matteo Ferrari Diego Dibitetto Giuseppe De Gregorio Vinay V. Eapen Chetan C. Rawal Federico Lazzaro Michael Tsabar Federica Marini James E. Haber Achille Pellicioli 《PLoS genetics》2015,11(1)
The Mre11-Rad50-Xrs2 nuclease complex, together with Sae2, initiates the 5′-to-3′ resection of Double-Strand DNA Breaks (DSBs). Extended 3′ single stranded DNA filaments can be exposed from a DSB through the redundant activities of the Exo1 nuclease and the Dna2 nuclease with the Sgs1 helicase. In the absence of Sae2, Mre11 binding to a DSB is prolonged, the two DNA ends cannot be kept tethered, and the DSB is not efficiently repaired. Here we show that deletion of the yeast 53BP1-ortholog RAD9 reduces Mre11 binding to a DSB, leading to Rad52 recruitment and efficient DSB end-tethering, through an Sgs1-dependent mechanism. As a consequence, deletion of RAD9 restores DSB repair either in absence of Sae2 or in presence of a nuclease defective MRX complex. We propose that, in cells lacking Sae2, Rad9/53BP1 contributes to keep Mre11 bound to a persistent DSB, protecting it from extensive DNA end resection, which may lead to potentially deleterious DNA deletions and genome rearrangements. 相似文献
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