Slx5/Slx8 Promotes Replication Stress Tolerance by Facilitating Mitotic Progression

Thu, Yee Mon; Riper, Susan K. Van; Higgins, Lee Ann; Zhang, Tianji; Becker, Jordan R.; Markowski, Todd W.; Nguyen, Hai Dang; Griffin, Timothy J.; Bielinsky, Anja‐Katrin

doi:10.1016/j.celrep.2016.04.017

Cited by 30 publications

(26 citation statements)

References 65 publications

(99 reference statements)

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“…In-gel trypsin digestion. In-gel trypsin digestion was performed according to a previously published procedure 53 . Briefly, gel pieces were cut into a size of approximately 2 mm 2 × 1 mm (thickness of the gel), washed with addition of wash solution (50 mM ammonium bicarbonate (pH 7.8) and 50% (v/v) acetonitrile) at room temperature for 15 min, and then aspirated.…”

Section: Preparation Of Samples For Mass Spectrometrymentioning

confidence: 99%

A soluble truncated tau species related to cognitive dysfunction is elevated in the brain of cognitively impaired human individuals

Liu

Smith

Montonye

et al. 2020

Sci Rep

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Neurofibrillary tangles are a pathological hallmark of Alzheimer's disease, and their levels correlate with the severity of cognitive dysfunction in humans. However, experimental evidence suggests that soluble tau species cause cognitive deficits and memory impairment. Our recent study suggests that caspase-2 (Casp2)-catalyzed tau cleavage at aspartate 314 mediates synaptic dysfunction and memory impairment in mouse and cellular models of neurodegenerative disorders. Δtau314, the C-terminallytruncated cleavage products, are soluble and present in human brain. In addition, levels of Δtau314 proteins are elevated in the brain of the cognitively impaired individuals compared to the cognitively normal individuals, indicating a possible role for Δtau314 proteins in cognitive deterioration. Here we show that (1) Δtau314 proteins are present in the inferior temporal gyrus of human brains; (2) Δtau314 proteins are generated from all six tau splicing isoforms, (3) levels of both Casp2 and Δtau314 proteins are elevated in cognitively impaired individuals compared to cognitively normal individuals, and (4) levels of Δtau314 proteins show a modest predictive value for dementia. These findings advance our understanding of the characteristics of Δtau314 proteins and their relevance to cognitive dysfunction and shed light on the contribution of Casp2-mediated Δtau314 production to cognitive deterioration.Tau is a soluble and unstructured protein, is enriched in neurons of the central nervous system (CNS), and plays an essential role in the formation and stabilization of microtubules to maintain normal neuronal structure and function 1,2 . In the human CNS, six isoforms of tau are generated by alternative splicing of exons 2, 3, or 10 of mRNA 3,4 . Tau is subjected to more than ten types of post-translational modifications (PTMs); under pathological conditions, the coordinated actions of multiple tau PTMs result in its dissociation from microtubules and intra-cellular aggregation to form neurofibrillary tangles (NFTs), a pathological hallmark of Alzheimer's disease (AD) (for review, see 5 ). As the burden of NFTs in a variety of brain regions correlate well with the severity of cognitive deficits of AD patients (for example, see 6-10 ), NFTs were assumed to be one of the major drivers of cognitive impairment. However, Gomez-Isla and colleagues observed that in the brain of individuals with AD, both the amount of neuron loss and the amount of NFTs in the disease-affected superior temporal sulcus correlate with the duration and severity of cognitive dysfunction, but the former exceeds the latter more than 7-fold. This suggests that neuronal loss, rather than NFTs, contributes directly to cognitive dysfunction in AD 11 . Further, several studies using tau transgenic mouse models have shown that synaptic function impairment and cognitive deficits

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Section: Preparation Of Samples For Mass Spectrometrymentioning

confidence: 99%

A soluble truncated tau species related to cognitive dysfunction is elevated in the brain of cognitively impaired human individuals

Liu

Smith

Montonye

et al. 2020

Sci Rep

Self Cite

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“…Relocalization of eroded telomeres to the nuclear pore relies on SUMOylation of telomeric components and RPA [45, 80]. Because a large number of proteins are SUMOylated during the DNA damage response (see for example [36, 83–85]), it is likely that more than one component contributes to signaling DSBs for relocalization, and an interesting possibility is that different targets are specialized for distinct damage sites and relocalization destinations. Further, given that SUMOylation is a common response during DSB repair, a threshold of SUMOylation might also need to be reached to trigger relocalization, perhaps as a result of persistent signaling at DSBs that are difficult to repair.…”

Section: Signaling Pathways and Mechanisms Responsible For Relocalizamentioning

confidence: 99%

Nuclear Dynamics of Heterochromatin Repair

et al. 2017

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Repairing double-strand breaks (DSBs) is particularly challenging in pericentromeric heterochromatin, where the abundance of repeated sequences exacerbates the risk of ectopic recombination and chromosome rearrangements. Recent studies in Drosophila cells revealed that faithful homologous recombination repair of heterochromatic DSBs relies on the relocalization of DSBs to the nuclear periphery before Rad51 recruitment. Here we summarize the exciting progress in understanding this pathway, including conserved responses in mammalian cells and surprising similarities with mechanisms available in yeast to deal with DSBs in other sites that are difficult to repair, including other repeated sequences. We will also point out some of the most important open questions in the field and emerging evidence suggesting that deregulating these pathways might have dramatic consequences for human health.

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“…The protein bands were visualized by Coomassie Brilliant Blue R-250 (Thermo Fisher Scientific, Waltham, MA, USA) and excised for protein identification. After in-gel trypsin digestion the peptide mixture was analyzed by capillary liquid chromatography-mass spectrometry (LC-MS) on an Eksigent 1D plus LC with a MicroAS autosampler (Dublin, Ireland) online with an Orbitrap Velos MS system (Thermo Fisher Scientific, Waltham, MA, USA) as previously described [16].…”

Section: Co-immunoprecipitation Of Sty1099mentioning

confidence: 99%

Transcriptional Profiling and Molecular Characterization of the yccT Mutant Link: A Novel STY1099 Protein with the Peroxide Stress Response and Cell Division of Salmonella enterica Serovar Enteritidis

Vidović

An³

et al. 2019

Biology

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Uncharacterized protein STY1099, encoded by the yccT gene, was previously identified as the most altered (i.e., upregulated) protein among the ZnO nanoparticle (NP) stimulon of Salmonella enterica serovar Enteritidis. Here we combined various stress response-related assays with functional genetics, global transcriptomic and proteomic analyses to characterize the yccT gene and its STY1099 product. Exposure of S. enterica Enteritidis to H2O2 (i.e., hydrogen peroxide) resulted in a significant (p < 0.0001) upregulation of the yccT gene, whereas exposure to paraquat (i.e., superoxide) did not alter the expression of the yccT gene. The ∆yccT mutant of S. enterica Enteritidis exposed to 0.75 mM H2O2, showed significantly reduced (p < 0.05) viability compared to the wild type strain. Further, comparative transcriptome analyses supported by Co-immunoprecipitation (Co-IP) assay revealed that STY1099 protein plays a role in redox homeostasis during the peroxide stress assault via involvement in the processes of respiratory nitrate reductase, oxidoreductase activities, cellular uptake and stress response. In addition, we found that the STY1099 protein has the monopolar subcellular location and that it interacts with key cell division proteins, MinD, and FtsH, as well as with a rod shape-determining protein MerB.

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Slx5/Slx8 Promotes Replication Stress Tolerance by Facilitating Mitotic Progression

Cited by 30 publications

References 65 publications

A soluble truncated tau species related to cognitive dysfunction is elevated in the brain of cognitively impaired human individuals

A soluble truncated tau species related to cognitive dysfunction is elevated in the brain of cognitively impaired human individuals

Nuclear Dynamics of Heterochromatin Repair

Transcriptional Profiling and Molecular Characterization of the yccT Mutant Link: A Novel STY1099 Protein with the Peroxide Stress Response and Cell Division of Salmonella enterica Serovar Enteritidis

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