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A chemical biology approach to decipher chromatin ubiquitylation by RNF168

Publications associées (32)

Decoding Chromatin Ubiquitylation: A Chemical Biology Perspective

Since Strahl and Allis proposed the "language of covalent histone modifications", a host of experimental studies have shed light on the different facets of chromatin regulation by epigenetic mechanisms. Initially proposed as a concept for controlling gene ...

Academic Press Ltd- Elsevier Science Ltd2024

The CRL5-SPSB3 ubiquitin ligase targets nuclear cGAS for degradation

Andrea Ablasser, Baptiste Claude André Guey, Jonathan Jean-Pierre Ricci, Pauline Ambre Melenec, Ying Liu, Pengbiao Xu, Chong Liu, Lingyun Li

Cyclic GMP-AMP synthase (cGAS) senses aberrant DNA during infection, cancer and inflammatory disease, and initiates potent innate immune responses through the synthesis of 2 ' 3 '-cyclic GMP-AMP (cGAMP)1-7. The indiscriminate activity of cGAS towards DNA d ...

Nature Portfolio2024

Oxidative Defect Detection Within Free and Packed DNA Systems: A Quantum Mechanical/Molecular Mechanics (QM/ MM) Approach

Ursula Röthlisberger

Base excision repair enzymes (BERs) detect and repair oxidative DNA damage with efficacy despite the small size of the defects and their often only minor structural impact. A charge transfer (CT) model for rapid scanning of DNA stretches has been evoked to ...

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Revealing chromatin-specific functions of histone deacylases

Beat Fierz, Carlos Moreno Yruela

Histone deacylases are erasers of Nε-acyl-lysine post-translational modifications and have been targeted for decades for the treatment of cancer, neurodegeneration and other disorders. Due to their relatively promiscuous activity on peptide substrates in v ...

2024

Inheritance of H3K9 methylation regulates genome architecture in Drosophila early embryos

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Constitutive heterochromatin is essential for transcriptional silencing and genome integrity. The establishment of constitutive heterochromatin in early embryos and its role in early fruitfly development are unknown. Lysine 9 trimethylation of histone H3 ( ...

Springernature2024

Investigating the intra-molecular and inter-molecular effects of post-translational modifications on intrinsically disordered protein regions and structured protein regions

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Post-translational modifications (PTMs) play a pivotal role in regulating protein structure, interaction, and function. Aberrant PTM patterns are associated with diseases. Moreover, individual PTMs have a complex interaction with each other, known as PTM c ...

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Ion Spectroscopy Reveals Structural Difference for Proteins Microhydrated by Retention and Condensation of Water

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Protein ubiquitin in its +7 charge state microhydrated by 5 and 10 water molecules has been interrogated in the gas phase by cold ion UV/IR spectroscopy. The complexes were formed either by condensing water onto the unfolded bare proteins in a temperature- ...

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Chromosome organization shapes replisome dynamics in Caulobacter crescentus

Suliana Manley, Laurent Casini, Chen Zhang

DNA replication in bacteria takes place on highly compacted chromosomes, where segregation, transcription, and repair must occur simultaneously. Within this dynamic environment, colocalization of sister replisomes has been observed in many bacterial specie ...

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Resolving bacterial cell biology: from replisome dynamics to cell wall synthesis

Chen Zhang

Bacteria are ubiquitous single cellular organisms. Compared to eukaryotic cells, bacteria have two unique characteristics: the membrane-less nucleoid and the cell wall built of peptidoglycan (PG). In most bacteria, a single circular chromosome is compacted ...

EPFL2024

Engineering novel protein interactions with therapeutic potential using deep learning-guided surface design

Anthony Marchand

Proteins are foundational biomolecules of life playing a crucial role in a myriad of biological processes. Their function often requires interplay with other biomolecules, including proteins themselves. Protein-protein interactions (PPIs) are essential for ...

EPFL2024

Preomic profile of BxPC-3 cells after treatment with BRC4

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BRCA2 and RAD51 are two proteins that play a central role in homologous recombination (HR) and DNA double strand break (DSB) repair. BRCA2 assists RAD51 fibrillation and defibrillation through binding with its eight BRC repeats, with BRC4 being one of the ...

ELSEVIER2023

Telomere protection against oxidative stress

Thu Trang Nguyen

Telomeres are nucleoprotein structures at the ends of linear chromosomes, being essential for the maintenance of genomic integrity. Telomeres have a unique structure which distinguishes chromosome termini from DNA damage sites. Shelterin complexes are the ...

EPFL2023

Pan-cancer atlas of somatic core and linker histone mutations

Sebastian Martin Waszak

Recent genomic data points to a growing role for somatic mutations altering core histone and linker histone-encoding genes in cancer. However, the prevalence and the clinical and biological implications of histone gene mutations in malignant tumors remain ...

2023

Regulation and impact of TERRA R-loops at human telomeres

Rita Valador Fernandes

Telomeres are the nucleoprotein structures found at the ends of linear chromosomes. They ensure that the termini of chromosomes are not inappropriately recognized as sites of DNA damage, and are therefore crucial for genome stability. In spite of the heter ...

EPFL2023

Development of multiplexed single-molecule imaging techniques to study chromatin invasion dynamics of chromatin effector proteins

Kristina Makasheva

DNA-binding proteins physically interact with the DNA and directly affect genomic functions. The eukaryotic genome is compacted into chromatin, limiting the DNA access to nuclear factors. In this Ph.D. thesis, I explored the dynamic mechanisms, that allow ...

EPFL2023

Coordination of protein synthesis and degradation in mammalian cells

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The cellular protein levels are determined by protein synthesis and turnover rates. Two processes are involved in the proteome's turnover in proliferating cells: protein degradation and dilution. In theory, maintaining the cellular proteome concentration, ...

EPFL2023

Landscapes of DNA Mechanics and Genomes

Thomas Antonin Zwahlen

The local physical properties - such as shape and flexibility - of the DNA double-helix is today widely believed to be influenced by nucleic acid sequence in a non-trivial way. Furthermore, there is strong evidence that these properties play a role in many ...

EPFL2023

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Ruxandra-Andreea Lambuta

Whole genome doubling (WGD) events are drivers of genetic innovation across vertebrate evolution. While generally detrimental to mammalian organisms, WGDs are crucial in the development of various plants and fungi, as well as for the terminal differentiati ...

EPFL2023

cgNA+: A sequence-dependent coarse-grain model of double-stranded nucleic acids

Rahul Sharma

DNA mechanics plays a crucial role in many biological processes, including nucleosome positioning and protein-DNA interactions. It is believed that nature employs epigenetic modifications in DNA to further regulate gene expression. Moreover, double-strande ...

EPFL2023

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

Rita Sarkis, Maria Younes

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