scholarly journals DNA viruses and the cellular DNA-damage response

2012 ◽  
Vol 93 (10) ◽  
pp. 2076-2097 ◽  
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.

scholarly journals Virus DNA Replication and the Host DNA Damage Response

2018 ◽  
Vol 5 (1) ◽  
pp. 141-164 ◽  
Author(s):  
Matthew D. Weitzman ◽  
Amélie Fradet-Turcotte
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Life Cycles ◽  
Dynamic Interactions ◽  
Dna Damage And Repair ◽  
Dna Viruses ◽  
Cellular Processes ◽  
Damage Response ◽  
Cellular Replication ◽  
Cellular Dna

Viral DNA genomes have limited coding capacity and therefore harness cellular factors to facilitate replication of their genomes and generate progeny virions. Studies of viruses and how they interact with cellular processes have historically provided seminal insights into basic biology and disease mechanisms. The replicative life cycles of many DNA viruses have been shown to engage components of the host DNA damage and repair machinery. Viruses have evolved numerous strategies to navigate the cellular DNA damage response. By hijacking and manipulating cellular replication and repair processes, DNA viruses can selectively harness or abrogate distinct components of the cellular machinery to complete their life cycles. Here, we highlight consequences for viral replication and host genome integrity during the dynamic interactions between virus and host.

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

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Stephen M. Rawlinson ◽  
Tianyue Zhao ◽  
Ashley M. Rozario ◽  
Christina L. Rootes ◽  
Paul J. McMillan ◽  
...  
Keyword(s):  
Dna Damage ◽  
Host Cell ◽  
Dna Damage Response ◽  
Cell Biology ◽  
Damage Response

scholarly journals High Fidelity Deep Sequencing Reveals No Effect of ATM, ATR, and DNA-PK Cellular DNA Damage Response Pathways on Adenovirus Mutation Rate

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 938 ◽  
Author(s):  
Risso-Ballester ◽  
Sanjuán
Keyword(s):  
Dna Damage ◽  
Protein Kinase ◽  
Dna Damage Response ◽  
Deep Sequencing ◽  
Molecular Mechanisms ◽  
Spontaneous Mutation ◽  
High Fidelity ◽  
Dna Viruses ◽  
Damage Response ◽  
Cellular Dna

Most DNA viruses exhibit relatively low rates of spontaneous mutation. However, the molecular mechanisms underlying DNA virus genetic stability remain unclear. In principle, mutation rates should not depend solely on polymerase fidelity, but also on factors such as DNA damage and repair efficiency. Most eukaryotic DNA viruses interact with the cellular DNA damage response (DDR), but the role of DDR pathways in preventing mutations in the virus has not been tested empirically. To address this goal, we serially transferred human adenovirus type 5 in cells in which the telangiectasia-mutated PI3K-related protein kinase (ATM), the ATM/Rad3-related (ATR) kinase, and the DNA-dependent protein kinase (DNA-PK) were chemically inactivated, as well as in control cells displaying normal DDR pathway functioning. High-fidelity deep sequencing of these viral populations revealed mutation frequencies in the order of one-millionth, with no detectable effect of the inactivation of DDR mediators ATM, ATR, and DNA-PK on adenovirus sequence variability. This suggests that these DDR pathways do not play a major role in determining adenovirus genetic diversity.

scholarly journals An Insight Into the Mechanism of Plant Organelle Genome Maintenance and Implications of Organelle Genome in Crop Improvement: An Update

2021 ◽  
Vol 9 ◽  
Author(s):  
Kalyan Mahapatra ◽  
Samrat Banerjee ◽  
Sayanti De ◽  
Mehali Mitra ◽  
Pinaki Roy ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Crop Improvement ◽  
Nuclear Genome ◽  
Genome Maintenance ◽  
Organelle Genome ◽  
Organellar Genomes ◽  
Damage Repair ◽  
Damage Response ◽  
Repair Pathways

Besides the nuclear genome, plants possess two small extra chromosomal genomes in mitochondria and chloroplast, respectively, which contribute a small fraction of the organelles’ proteome. Both mitochondrial and chloroplast DNA have originated endosymbiotically and most of their prokaryotic genes were either lost or transferred to the nuclear genome through endosymbiotic gene transfer during the course of evolution. Due to their immobile nature, plant nuclear and organellar genomes face continuous threat from diverse exogenous agents as well as some reactive by-products or intermediates released from various endogenous metabolic pathways. These factors eventually affect the overall plant growth and development and finally productivity. The detailed mechanism of DNA damage response and repair following accumulation of various forms of DNA lesions, including single and double-strand breaks (SSBs and DSBs) have been well documented for the nuclear genome and now it has been extended to the organelles also. Recently, it has been shown that both mitochondria and chloroplast possess a counterpart of most of the nuclear DNA damage repair pathways and share remarkable similarities with different damage repair proteins present in the nucleus. Among various repair pathways, homologous recombination (HR) is crucial for the repair as well as the evolution of organellar genomes. Along with the repair pathways, various other factors, such as the MSH1 and WHIRLY family proteins, WHY1, WHY2, and WHY3 are also known to be involved in maintaining low mutation rates and structural integrity of mitochondrial and chloroplast genome. SOG1, the central regulator in DNA damage response in plants, has also been found to mediate endoreduplication and cell-cycle progression through chloroplast to nucleus retrograde signaling in response to chloroplast genome instability. Various proteins associated with the maintenance of genome stability are targeted to both nuclear and organellar compartments, establishing communication between organelles as well as organelles and nucleus. Therefore, understanding the mechanism of DNA damage repair and inter compartmental crosstalk mechanism in various sub-cellular organelles following induction of DNA damage and identification of key components of such signaling cascades may eventually be translated into strategies for crop improvement under abiotic and genotoxic stress conditions. This review mainly highlights the current understanding as well as the importance of different aspects of organelle genome maintenance mechanisms in higher plants.

scholarly journals The heterogeneity of the DNA damage response landscape determines patient outcomes in ovarian cancer

2021 ◽  
Author(s):  
Thomas Walker ◽  
Zahra Faraahi ◽  
marcus price ◽  
Amy Hawarden ◽  
Catlin Waddell ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Ex Vivo ◽  
Single Strand ◽  
Cellular Growth ◽  
Response To Chemotherapy ◽  
Damage Response ◽  
Repair Pathways ◽  
Non Homologous End Joining

Defective DNA damage response (DDR) pathways allow cancer cells to accrue genomic aberrations and evade normal cellular growth checkpoints. Defective DDR also determines response to chemotherapy. However, the interaction and overlap between the two double strand repair pathways and the three single strand repair pathways is complex, and has remained poorly understood. Here we show that, in ovarian cancer, a disease hallmarked by chromosomal instability, explant cultures show a range of DDR abrogation patterns. Defective homologous recombination (HR) and non-homologous end joining (NHEJ) are near mutually exclusive with HR deficient (HRD) cells showing increased abrogation of the single strand repair pathways compared to NHEJ defective cells. When combined with global markers of DNA damage, including mitochondrial membrane functionality and reactive oxygen species burden, the pattern of DDR abrogation allows the construction of DDR signatures which are predictive of both ex vivo cytotoxicity, and more importantly, patient outcome.

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