Dampens the DNA Damage Response


In eukaryotic cells both normal metabolic activities and environmental factors such as UV radiation can cause DNA lesions or mutations. The ability of a cell to restore integrity to its genome is vital, and depends on a signaling cascade called the DNA damage response (DDR) that both senses and responds to the assaults. Bacterial infection is one such assault, but its effect on the DDR of the invaded cell remains elusive. Here we used the bacterial pathogen Listeria monocytogenes to study its effect on host DNA damage and its impact on the DDR. Our results show that although Listeria is able to induce DNA damage, the ensuing response is surprisingly low, demonstrating that this bacterium is able to dampen the DDR. We have also shown that the listerial toxin listeriolysin O (LLO) is responsible for the observed block in the DDR. In fact, we find that LLO induces protein degradation of the main DNA damage sensor, Mre11, thereby blocking downstream signaling. Furthermore, we have studied the impact of mutating the DDR on the infectious process and find that it negatively regulates infection with Listeria. In conclusion, our findings reveal that dampening of the DDR is crucial for a productive infection.


Vyšlo v časopise: Dampens the DNA Damage Response. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004470
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.ppat.1004470

Souhrn

In eukaryotic cells both normal metabolic activities and environmental factors such as UV radiation can cause DNA lesions or mutations. The ability of a cell to restore integrity to its genome is vital, and depends on a signaling cascade called the DNA damage response (DDR) that both senses and responds to the assaults. Bacterial infection is one such assault, but its effect on the DDR of the invaded cell remains elusive. Here we used the bacterial pathogen Listeria monocytogenes to study its effect on host DNA damage and its impact on the DDR. Our results show that although Listeria is able to induce DNA damage, the ensuing response is surprisingly low, demonstrating that this bacterium is able to dampen the DDR. We have also shown that the listerial toxin listeriolysin O (LLO) is responsible for the observed block in the DDR. In fact, we find that LLO induces protein degradation of the main DNA damage sensor, Mre11, thereby blocking downstream signaling. Furthermore, we have studied the impact of mutating the DDR on the infectious process and find that it negatively regulates infection with Listeria. In conclusion, our findings reveal that dampening of the DDR is crucial for a productive infection.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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