The inflammasome sensor NLRP3 interacts with REV7 to maintain genome integrity through homologous recombination DOI Creative Commons

Delphine Burlet,

Md. Muntaz Khan,

Sabine Hacot

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 28, 2024

ABSTRACT DNA double strand break (DSB) is a highly toxic lesion that can generate genome instability, major source of tumorigenesis. DSBs are mainly repaired by non-homologous end joining (NHEJ) or homologous recombination (HR). The selection the DSB repair pathway primarily depends on resection ends. Indeed, HR initiated at generating 3’ single stranded extension. shieldin complex prevents fostering toward NHEJ. Here, we reveal inflammasome sensor NLRP3 facilitates to promote in an inflammasome-independent manner. Strikingly, silencing decreases efficiency, as evidenced RAD51 foci and functional assays. Mechanistically, describe interacts with REV7, subunit complex, its depletion increases REV7 recruitment IR-induced DSBs. Similar cancer cells harboring mutated genes, find deficient sensitive PARP inhibitors (PARPi) exhibit epistatic relationship BRCA1 deficiency. Remarkably, loss NLRP3-depleted induces PARPi resistance restoring HR. This study unravels crucial role innate immune receptor regulating pathways maintain integrity.

Язык: Английский

p53-regulated non-apoptotic cell death pathways and their relevance in cancer and other diseases DOI
Yanqing Liu, Brent R. Stockwell, Xuejun Jiang

и другие.

Nature Reviews Molecular Cell Biology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 9, 2025

Язык: Английский

Процитировано

4

Crosstalk between inflammasome sensors and DNA damage response pathways DOI Open Access

Delphine Burlet,

Anne‐Laure Huber, Agnès Tissier

и другие.

FEBS Journal, Год журнала: 2024, Номер unknown

Опубликована: Янв. 25, 2024

Eukaryotic cells encounter diverse threats jeopardizing their integrity, prompting the development of defense mechanisms against these stressors. Among mechanisms, inflammasomes are well‐known for roles in coordinating inflammatory response infections. Extensive research has unveiled multifaceted involvement cellular processes beyond inflammation. Recent studies emphasize intricate relationship between inflammasome and DNA damage (DDR). They highlight how DDR participates activation reciprocal impact on genome integrity preservation. Moreover, novel functions sensors pathways have emerged, broadening our understanding roles. Finally, this review delves into identifying common signals that drive alongside cues response, offering potential insights shared regulatory critical processes.

Язык: Английский

Процитировано

5

Role of Lipopolysaccharides in the Inflammation and Pyroptosis of Alveolar Epithelial Cells in Acute Lung Injury and Acute Respiratory Distress Syndrome DOI Creative Commons
Xiao Li Shen,

Linglin He,

Wanru Cai

и другие.

Journal of Inflammation Research, Год журнала: 2024, Номер Volume 17, С. 5855 - 5869

Опубликована: Авг. 1, 2024

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a spectrum of common critical conditions characterized by damage death alveolar epithelial cells (AECs). Pyroptosis is form programmed cell with inflammatory characteristics, activation pyroptosis markers has been observed in AECs patients ALI/ARDS. Lipopolysaccharides (LPS) possess strong pro-inflammatory effects are crucial pathological factor leading to ALI animals. In LPS-induced models, undergo pyroptosis. However, physiologically pathologically relevant concentrations LPS lead minor on AEC viability minimal induction cytokine release vitro do not induce classical Nevertheless, can enter the cytoplasm directly non-classical when assisted extracellular vesicles from bacteria, HMGB1, pathogens. this review, we have explored concerning inflammation, viability, pyroptosis, analyzing key factors that influence actions. Notably, highlight intricate response within framework ARDS, emphasizing variable Despite vitro, under specific conditions, presenting potential pathways for therapeutic intervention. Collectively, understanding these mechanisms development targeted treatments mitigate responses ALI/ARDS, thereby enhancing patient outcomes severe conditions.

Язык: Английский

Процитировано

4

Inflammasome protein scaffolds the DNA damage complex during tumor development DOI
Cheng Shen, Abhimanu Pandey, Daniel Enosi Tuipulotu

и другие.

Nature Immunology, Год журнала: 2024, Номер 25(11), С. 2085 - 2096

Опубликована: Окт. 14, 2024

Язык: Английский

Процитировано

2

The Co-Localization of NLRP3 and ASC Specks Does Not Automatically Entail NLRP3 Inflammasome Functionality in PDAC Cell Lines DOI Creative Commons
Heléne Lindholm, Matthew Herring, Maria Faresjö

и другие.

International Journal of Translational Medicine, Год журнала: 2024, Номер 4(2), С. 224 - 237

Опубликована: Март 30, 2024

The NLRP3 inflammasome is an important mediator of the host inflammatory response, and downregulation inflammation in cancer treatment. Here, we investigated four different pancreatic ductal adenocarcinoma (PDAC) cell lines, AsPC-1, BxPC-3, CFPAC-1 Panc-1, with regards to formation cytokine secretion. ASC specks were observed all lines investigated, but AsPC-1 was only cell-line co-localization anti-ASC anti-NLRP3 spontaneously formed multiple inflammasomes per cell. not accompanied by IL-1β release nor significant IL-18 release. BxPC-3 displayed relatively high expression inflammasome-related genes IL1B CASP1 had highest levels IL1β IL18 secretion amount ASC. inflammasome-associated PYCARD up-regulated PDAC primary tumors compared normal tissue, tumor IL18, correlated low patient survival. We have shown that display variations their gene readouts. conclude spontaneous speck possible cells are does automatically entail function.

Язык: Английский

Процитировано

0

The inflammasome sensor NLRP3 interacts with REV7 to maintain genome integrity through homologous recombination DOI Creative Commons

Delphine Burlet,

Md. Muntaz Khan,

Sabine Hacot

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 28, 2024

ABSTRACT DNA double strand break (DSB) is a highly toxic lesion that can generate genome instability, major source of tumorigenesis. DSBs are mainly repaired by non-homologous end joining (NHEJ) or homologous recombination (HR). The selection the DSB repair pathway primarily depends on resection ends. Indeed, HR initiated at generating 3’ single stranded extension. shieldin complex prevents fostering toward NHEJ. Here, we reveal inflammasome sensor NLRP3 facilitates to promote in an inflammasome-independent manner. Strikingly, silencing decreases efficiency, as evidenced RAD51 foci and functional assays. Mechanistically, describe interacts with REV7, subunit complex, its depletion increases REV7 recruitment IR-induced DSBs. Similar cancer cells harboring mutated genes, find deficient sensitive PARP inhibitors (PARPi) exhibit epistatic relationship BRCA1 deficiency. Remarkably, loss NLRP3-depleted induces PARPi resistance restoring HR. This study unravels crucial role innate immune receptor regulating pathways maintain integrity.

Язык: Английский

Процитировано

0