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Cullin-RING ubiquitin E3 ligase regulation by the COP9 signalosome

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The CRL5-SPSB3 ubiquitin ligase targets nuclear cGAS for degradation

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

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

A chemical biology approach to decipher chromatin ubiquitylation by RNF168

Pauline Franz

DNA damage signaling following DNA double-strand breaks (DSBs) involves numerous regulating proteins, which dynamically recognize ('read') and alter ('write' or 'erase') histone post-translational modifications (PTMs). Among these PTMs, the ubiquitin syste ...

EPFL2024

Microsecond Time-Resolved Cryo-Electron Microscopy

Oliver Florian Harder

Recently, single-particle cryo-electron microscopy emerged as a technique capable of determining protein structures at near-atomic resolution and resolving protein dynamics with a temporal resolution ranging from second to milliseconds. This thesis describ ...

EPFL2024

Molecular mechanism of plasmid elimination by the DdmDE defense system

Melanie Blokesch, Sandrine Stutzmann, David William Adams, Laurie Righi

Seventh pandemic Vibrio cholerae strains contain two pathogenicity islands that encode the DNA defense modules DdmABC and DdmDE. Here we use cryogenic electron microscopy to reveal the mechanistic basis for plasmid defense by DdmDE. A structure of the DdmD ...

2024

In Situ and Time-Resolved Transmission Electron Microscopy of Nanoscale Processes

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Observing the fast dynamics of nanoscale systems is crucial in order to understand and ultimately control their behavior. Characterizing these dynamic processes requires techniques with atomic spatial resolution and a temporal resolution that matches the t ...

EPFL2023

Towards near-atomic resolution imaging of microsecond nanoscale dynamics

Gabriele Bongiovanni

Time-resolved electron microscopy has made significant progress in recent years, with some groups now working on instruments that offer attosecond temporal resolution. While much of the research in the field revolves around the improvement of temporal reso ...

EPFL2023

Rapid melting and revitrification as an approach to microsecond time-resolved cryo-electron microscopy

Marcel Drabbels, Ulrich Lorenz, Pavel Olshin, Jonathan Mark Voss, Oliver Florian Harder

Proteins typically undergo dynamics on the microsecond to millisecond timescale, which is much faster than the time resolution of cryo-electron microscopy. Here, we propose a novel approach for microsecond time-resolved cryo-electron microscopy that involv ...

2021

A scalable CRISPR/Cas9-based fluorescent reporter assay to study DNA double-strand break repair choice

Stephanie Jocelyne Sungalee

Double-strand breaks (DSBs) are the most toxic type of DNA lesions. Cells repair these lesions using either end protection- or end resection-coupled mechanisms. To study DSB repair choice, we present the Color Assay Tracing-Repair (CAT-R) to simultaneously ...

2020

DNA repair protein Rad18 restricts LINE-1 mobility

Priscilla Turelli

Long interspersed element-1 (LINE-1, L1) is a mobile genetic element comprising about 17% of the human genome. L1 utilizes an endonuclease to insert L1 cDNA into the target genomic DNA, which induces double-strand DNA breaks in the human genome and activat ...

NATURE PUBLISHING GROUP2018

Miniaturizing EM Sample Preparation: Opportunities, Challenges, and "Visual Proteomics"

Henning Paul-Julius Stahlberg, Anastasia Syntychaki

This review compares and discusses conventional versus miniaturized specimen preparation methods for transmission electron microscopy (TEM). The progress brought by direct electron detector cameras, software developments and automation have transformed tra ...

Wiley-Blackwell2018

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