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Concept

Poly(ADP-ribose) polymérase

Publications associées (17)

Urtica dioica Leaf Infusion Enhances the Sensitivity of Triple-Negative Breast Cancer Cells to Cisplatin Treatment

Rita Sarkis

Urtica dioica (UD) has been widely used in traditional medicine due to its therapeutic benefits, including its anticancer effects. Natural compounds have a promising potential when used in combination with chemotherapeutic drugs. The present study explores ...

MDPI2023

Relief of ParB autoinhibition by parS DNA catalysis and recycling of ParB by CTP hydrolysis promote bacterial centromere assembly

Paolo De Los Rios, Stefano Zamuner

Three-component ParABS systems are widely distributed factors for plasmid partitioning and chromosome segregation in bacteria. ParB acts as adaptor protein between the 16-base pair centromeric parS DNA sequences and the DNA segregation proteins ParA and Sm ...

AMER ASSOC ADVANCEMENT SCIENCE2021

PRDX1 Counteracts Catastrophic Telomeric Cleavage Events That Are Triggered by DNA Repair Activities Post Oxidative Damage

Joachim Lingner, Wareed Ahmed

Telomeres are prone to damage inflicted by reactive oxygen species (ROS). Oxidized telomeric DNA and nucleotide substrates inhibit telomerase, causing telomere shortening. In addition, ROS can induce telomeric single-strand DNA breaks (SSBs). The peroxired ...

2020

Human shelterin protein POT1 prevents severe telomere instability induced by homology-directed DNA repair

Joachim Lingner, Galina Glousker, Anna-Sophia Briod

The evolutionarily conserved POT1 protein binds single-stranded G-rich telomeric DNA and has been implicated in contributing to telomeric DNA maintenance and the suppression of DNA damage checkpoint signaling. Here, we explore human POT1 function through g ...

WILEY2020

The Gene-Regulatory Footprint of Aging Highlights Conserved Central Regulators

Johan Auwerx, Maroun Bou Sleiman, Richardus Houtkooper, Xu Wang, Pooja Jha

Many genes and pathways have been linked to aging, yet our understanding of underlying molecular mechanisms is still lacking. Here, we measure changes in the transcriptome, histone modifications, and DNA methylome in three metabolic tissues of adult and ag ...

2020

The telomeric DNA damage response: Insights into telomere compaction and identification of novel damage signaling factors

Aleksandra Vancevska

Telomeres are dynamic nucleo-protein structures capping the ends of all eukaryotic chromosomes. Together with telomerase, they counteract replication-dependent telomere attrition. Additionally, they disguise the linear ends of the chromosome from the DNA d ...

EPFL2018

Telomeric states in cancer development

Jana Majerská

Telomere dysfunction can unleash genome instability or permanently arrest cell proliferation, and thereby contribute to the processes of cancer and aging. Proper telomere function relies on many proteins that form part of its structure. Some telomeric prot ...

EPFL2018

NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells

Johan Auwerx, Carlos Canto Alvarez, Joanna Ratajczak

NAD(+) is a vital redox cofactor and a substrate required for activity of various enzyme families, including sirtuins and poly(ADP-ribose) polymerases. Supplementation with NAD(+) precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide ribosi ...

Nature Publishing Group2016

No DDRama at chromosome ends: TRF2 takes centre stage

Liuh-Yow Chen, Antonio Porro, Sascha Feuerhahn

Telomeres are nucleoprotein structures capping the natural termini of eukaryotic linear chromosomes. Telomeres possess an inherent ability to circumvent the activation of a full-blown DNA damage response (DDR), and hence fusion reactions, by limiting inapp ...

Elsevier Science London2015

Pharmacological Inhibition of Poly(ADP-Ribose) Polymerases Improves Fitness and Mitochondrial Function in Skeletal Muscle

Johan Auwerx, Kristina Schoonjans, Carlos Canto Alvarez, Laurent Mouchiroud, Evan Graehl Williams, Norman Lionel Moullan, Hongbo Zhang, Keir Joe Menzies, Eija Riitta Pirinen, Laia Morato Fornaguera

We previously demonstrated that the deletion of the poly(ADP-ribose) polymerase (Parp)-1 gene in mice enhances oxidative metabolism, thereby protecting against diet-induced obesity. However, the therapeutic use of PARP inhibitors to enhance mitochondrial f ...

Cell Press2014

Functional characterization of the TERRA transcriptome at damaged telomeres

Joachim Lingner, Jacques Rougemont, Antonio Porro, Sascha Feuerhahn

Telomere deprotection occurs during tumorigenesis and aging upon telomere shortening or loss of the telomeric shelterin component TRF2. Deprotected telomeres undergo changes in chromatin structure and elicit a DNA damage response (DDR) that leads to cellul ...

Nature Publishing Group2014

Molecular basis of telomere syndrome caused by CTC1 mutations

Joachim Lingner, Liuh-Yow Chen, Jana Majerská

Mutations in CTC1 lead to the telomere syndromes Coats Plus and dyskeratosis congenita (DC), but the molecular mechanisms involved remain unknown. CTC1 forms with STN1 and TEN1 a trimeric complex termed CST, which binds ssDNA, promotes telomere DNA synthes ...

Cold Spring Harbor Laboratory Press2013

Cytotoxic gold compounds: synthesis, biological characterization and investigation of their inhibition properties of the zinc finger protein PARP-1

Michael Graetzel, Shaik Mohammed Zakeeruddin, Rosario Scopelliti, Angela Casini, Fabio Edafe

The new gold(III) complexes: [Au{2-(2'-pyridyl) imidazolate}Cl-2] and [Au{2,6-bis(2'-benzimidazolate) pyridine}(OCOCH3)] and the mono-and binuclear gold(I) complexes: Au{2-(2'-pyridyl) imidazole} (PPh3), [Au(2-phenylimidazolate)(DAPTA)] (DAPTA = 3,7 ...

Royal Society of Chemistry2012

Interference between PARPs and SIRT1: a novel approach to healthy ageing?

Johan Auwerx, Carlos Canto Alvarez

Poly(ADP-ribosyl) polymerases (PARPs) have traditionally been linked to chromosome maintenance and DNA repair. Recent findings identify PARPs as key modulators of metabolism through their influence on SIRT1 activity, hinting to a possible role of PARPs as ...

2011

Organometallic antitumour agents with alternative modes of action

Paul Joseph Dyson, Christian Hartinger, Angela Casini, Alexey Nazarov

The therapeutic index of drugs that target DNA, a ubiquitous target present in nearly all cells, is low. Nevertheless, DNA has remained the primary target for medicinal chemists developing metal-based anticancer drugs, although DNA has been essentially aba ...

2010

Telomere length homeostasis

Joachim Lingner

The physical ends of chromosomes, known as telomeres, protect chromosome ends from nucleolytic degradation and DNA repair activities. Conventional DNA replication enzymes lack the ability to fully replicate telomere ends. In addition, nucleolytic activitie ...

Springer-Verlag2006

DNA damage sensors ATM, ATR, DNA-PKcs, and PARP-1 are dispensable for human immunodeficiency virus type 1 integration

Didier Trono, Priscilla Turelli

Integration of a DNA copy of the viral RNA genome is a crucial step in the life cycle of human immunodeficiency virus type 1 (HIV-1) and other retroviruses. While the virally encoded integrase is key to this process, cellular factors yet to be characterize ...

American Society for Microbiology2005