Jean‐Philippe Gagné

ZIPPing the gaps: A new class of zinc finger proteins orchestrates the DNA damage response

Louis Nonfoux, Jean‐Philippe Gagné, Bong Gu Kang, Sung-Ung Kang et autres

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Nucleoplasmic Lamin A/C controls replication fork restart upon stress by modulating local H3K9me3 and ADP-ribosylation levels

Veronica Cherdyntseva, Daniel González‐Acosta, Patricia Ubieto‐Capella, M. do C. Rodrigues et autres

Mild replication interference is a consolidated strategy for cancer chemotherapy. Tolerance to mild replication stress (RS) relies on active fork slowing, mediated by transient fork reversal and RECQ1-assisted restart, and modulated by PARP1 and nuclear architectural components via yet-elusive mechanisms. We combined …

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CHD6 has poly(ADP-ribose)- and DNA-binding domains and regulates PARP1/2-trapping inhibitor sensitivity via abasic site repair

Luc Provencher, Wilson Nartey, Peter M. Brownlee, Jean‐Philippe Gagné et autres

To tolerate oxidative stress, cells enable DNA repair responses often sensitive to poly(ADP-ribose) (PAR) polymerase 1 and 2 (PARP1/2) inhibition—an intervention effective against cancers lacking BRCA1/2. Here, we demonstrate that mutating the CHD6 chromatin remodeler sensitizes cells to PARP1/2 inhibitors in a …

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Nucleoplasmic Lamin A/C controls replication fork restart upon stress by modulating local H3K9me3 and ADP-ribosylation levels

Veronica Cherdyntseva, Selin Adakli, Jean‐Philippe Gagné, Moses Aouami et autres

Abstract Mild replication interference is a consolidated strategy for cancer chemotherapy. Tolerance to mild replication stress (RS) relies on active fork slowing, mediated by transient fork reversal and RECQ1-assisted restart, and modulated by PARP1 and nuclear architectural components via yet-elusive mechanisms. We …

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Proteomic study identifies Aurora-A–mediated regulation of alternative splicing through multiple splicing factors

Arun Prasath Damodaran, Olivia Gavard, Jean‐Philippe Gagné, Malgorzata Ewa Rogalska et autres

The cell cycle regulator Aurora-A kinase presents an attractive target for cancer therapies, though its inhibition is also associated with toxic side effects. To gain a more nuanced understanding of Aurora-A function, we applied shotgun proteomics to identify 407 specific protein partners, …

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pADP-ribosylation regulates the cytoplasmic localization, cleavage, and pro-apoptotic function of HuR

Kholoud Ashour, Sujitha Sali, Ali H. Aldoukhi, Derek T. Hall et autres

HuR (ElavL1) is one of the main post-transcriptional regulators that determines cell fate. Although the role of HuR in apoptosis is well established, the post-translational modifications that govern this function remain elusive. In this study, we show that PARP1/2-mediated poly(ADP)-ribosylation (PARylation) is …

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Poly( ADP ‐ribose) mediates bioenergetic defects and redox imbalance in neurons following oxygen and glucose deprivation

Mohammed Iqbal Hossain, Jun Hee Lee, Jean‐Philippe Gagné, Junaid H. Khan et autres

PARP-1 over-activation results in cell death via excessive PAR generation in different cell types, including neurons following brain ischemia. Glycolysis, mitochondrial function, and redox balance are key cellular processes altered in brain ischemia. Studies show that PAR generated after PARP-1 over-activation can …

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Tankyrase-1 regulates RBP-mediated mRNA turnover to promote muscle fiber formation

Souad Mubaid, Brenda Janice Sánchez, Rinad Algehani, Viktoriia Skopenkova et autres

Poly(ADP-ribosylation) (PARylation) is a post-translational modification mediated by a subset of ADP-ribosyl transferases (ARTs). Although PARylation-inhibition based therapies are considered as an avenue to combat debilitating diseases such as cancer and myopathies, the role of this modification in physiological processes such as …

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ZNF432 stimulates PARylation and inhibits DNA resection to balance PARPi sensitivity and resistance

Julia A. O’Sullivan, Charu Kothari, Marie‐Christine Caron, Jean‐Philippe Gagné et autres

Zinc finger (ZNF) motifs are some of the most frequently occurring domains in the human genome. It was only recently that ZNF proteins emerged as key regulators of genome integrity in mammalian cells. In this study, we report a new role for …

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pADP-ribosylation Regulates the Cytoplasmic Localization, Cleavage and Pro-apoptotic Function of HuR

Kholoud Ashour, Derek T. Hall, Souad Mubaid, Sandrine Busque et autres

Abstract HuR (ElavL1) is one of the main posttranscriptional regulators that determines cell fate. While the role of HuR in apoptosis is well-established, the posttranslational modifications that governs this function remain elusive. In this study we show that PARP1/2-mediated poly(ADP)-ribosylation (PARylation) is …

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The dynamic process of covalent and non-covalent PARylation in the maintenance of genome integrity: a focus on PARP inhibitors

Adèle Beneyton, Louis Nonfoux, Jean‐Philippe Gagné, Amélie Rodrigue et autres

Poly(ADP-ribosylation) (PARylation) by poly(ADP-ribose) polymerases (PARPs) is a highly regulated process that consists of the covalent addition of polymers of ADP-ribose (PAR) through post-translational modifications of substrate proteins or non-covalent interactions with PAR via PAR binding domains and motifs, thereby reprogramming their …

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Poly(ADP-ribose) mediates bioenergetic defects and redox imbalance in neurons following oxygen and glucose deprivation

Mohammed Iqbal Hossain, Jun Hee Lee, Jean‐Philippe Gagné, Junaid Ali Khan et autres

Abstract PARP-1 over-activation results in cell death via excessive PAR generation in different cell types, including neurons following brain ischemia. Glycolysis, mitochondrial function, and redox balance are key cellular processes altered in brain ischemia. Studies show that PAR generated after PARP-1 over-activation …

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