Viral regulation of host cell biology by hijacking of the nucleolar DNA-damage response

Cells have developed response systems to constantly monitor environmental changes and accordingly adjust growth, differentiation, and cellular stress programs. The evolutionarily conserved, nutrient-responsive, mechanistic target of rapamycin signaling (mTOR) pathway coordinates basic anabolic and catabolic cellular processes such as gene transcription, protein translation, autophagy, and metabolism, and is directly implicated in cellular and organismal aging as well as age-related diseases. mTOR mediates these processes in response to a broad range of inputs such as oxygen, amino acids, hormones, and energy levels, as well as stresses, including DNA damage. Here, we briefly summarize data relating to the interplays of the mTOR pathway with DNA damage response pathways in fission yeast, a favorite model in cell biology, and how these interactions shape cell decisions, growth, and cell-cycle progression. We, especially, comment on the roles of caffeine-mediated DNA-damage override. Understanding the biology of nutrient response, DNA damage and related pharmacological treatments can lead to the design of interventions towards improved cellular and organismal fitness, health, and survival.

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Trichodysplasia spinulosa polyomavirus small T antigen synergistically modulates S6 protein translation and DNA damage response pathways to shape host cell environment

Virus Genes ◽

10.1007/s11262-021-01880-7 ◽

2022 ◽

Author(s):

Deepika Narayanan ◽

Danyal Tahseen ◽

Brooke R. Bartley ◽

Stephen A. Moore ◽

Rebecca Simonette ◽

...

Keyword(s):

Dna Damage ◽

Host Cell ◽

Dna Damage Response ◽

Protein Translation ◽

T Antigen ◽

Damage Response ◽

Small T Antigen

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DNA viruses and the cellular DNA-damage response

Journal of General Virology ◽

10.1099/vir.0.044412-0 ◽

2012 ◽

Vol 93 (10) ◽

pp. 2076-2097 ◽

Cited By ~ 99

Author(s):

Andrew S. Turnell ◽

Roger J. Grand

Keyword(s):

Dna Damage ◽

Host Cell ◽

Virus Replication ◽

Dna Damage Response ◽

Cell Damage ◽

Simian Virus 40 ◽

Life Cycles ◽

Dna Viruses ◽

Damage Response ◽

Repair Pathways

It is clear that a number of host-cell factors facilitate virus replication and, conversely, a number of other factors possess inherent antiviral activity. Research, particularly over the last decade or so, has revealed that there is a complex inter-relationship between viral infection and the host-cell DNA-damage response and repair pathways. There is now a realization that viruses can selectively activate and/or repress specific components of these host-cell pathways in a temporally coordinated manner, in order to promote virus replication. Thus, some viruses, such as simian virus 40, require active DNA-repair pathways for optimal virus replication, whereas others, such as adenovirus, go to considerable lengths to inactivate some pathways. Although there is ever-increasing molecular insight into how viruses interact with host-cell damage pathways, the precise molecular roles of these pathways in virus life cycles is not well understood. The object of this review is to consider how DNA viruses have evolved to manage the function of three principal DNA damage-response pathways controlled by the three phosphoinositide 3-kinase (PI3K)-related protein kinases ATM, ATR and DNA-PK and to explore further how virus interactions with these pathways promote virus replication.

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Viral hijacking of the nucleolar DNA-damage response machinery: a novel mechanism to regulate host cell biology

10.1101/219071 ◽

2017 ◽

Author(s):

Stephen M. Rawlinson ◽

Tianyue Zhao ◽

Ashley M. Rozario ◽

Christina L. Rootes ◽

Paul J. McMillan ◽

...

Keyword(s):

Dna Damage ◽

Dna Damage Response ◽

Cell Biology ◽

Matrix Protein ◽

Protein A ◽

Super Resolution ◽

Host Cells ◽

Treacher Collins Syndrome ◽

Damage Response ◽

Pathogenic Viruses

ABSTRACTRecent landmark studies indicate that nucleoli play critical roles in the DNA-damage response (DDR) via interaction of DDR machinery including NBS1 with nucleolar Treacle protein, a key mediator of ribosomal RNA (rRNA) transcription and processing, implicated in Treacher-Collins syndrome. Here, using proteomics, confocal/super-resolution imaging, and infection under BSL-4 containment, we present the first report that this nucleolar DDR pathway is targeted by infectious pathogens. We find that Treacle has antiviral activity, but that matrix protein of Henipaviruses and P3 protein of rabies virus, highly pathogenic viruses of the order Mononegavirales, interact with Treacle and inhibit its function, thereby silencing rRNA biogenesis, consistent with mimicking NBS1-Treacle interaction during a DDR. These data identify a novel mechanism for viral modulation of host cells by appropriating the nucleolar DDR; this appears to have developed independently in different viruses, and represents, to our knowledge, the first direct intra-nucleolar function for proteins of any mononegavirus.

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