Chromosome organization shapes replisome dynamics in Caulobacter crescentus

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PR-DUB preserves Polycomb repression by preventing excessive accumulation of H2Aub1, an antagonist of chromatin compaction

Beat Fierz, Iuliia Boichenko

The Polycomb repressive complexes PRC1, PRC2, and PR-DUB repress target genes by modifying their chromatin. In Drosophila, PRC1 compacts chromatin and monoubiquitinates histone H2A at lysine 118 (H2Aub1), whereas PR-DUB is a major H2Aub1 deubiquitinase, bu ...

2022

Allosteric control of type I-A CRISPR-Cas3 complexes and establishment as effective nucleic acid detection and human genome editing tools

Henning Paul-Julius Stahlberg, Dongchun Ni

Type I CRISPR-Cas systems typically rely on a two-step process to degrade DNA. First, an RNA-guided complex named Cascade identifies the complementary DNA target. The helicase-nuclease fusion enzyme Cas3 is then recruited in trans for processive DNA degrad ...

CELL PRESS2022

TFIIH moonlighting at telomeres

Joachim Lingner, Galina Glousker

Although telomeres are essential for chromosome stability, they represent fragile structures in our genome. Telomere shortening occurs during aging in cells lacking telomerase due to the end replication problem. In addition, recent work uncovered that the ...

COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT2022

Principles of checkpoint override

Ahmad Sadeghi

Why biological quality-control systems fail is often mysterious. Specifically, checkpoints such as the DNA damage checkpoint or the spindle assembly checkpoint are overriden after prolonged arrests allowing cells to continue dividing despite the continued ...

EPFL2022

Preexisting Heterogeneity of Inducible Nitric Oxide Synthase Expression Drives Differential Growth of Mycobacterium tuberculosis in Macrophages

John McKinney, Chiara Toniolo, Ophélie Rutschmann

Mycobacterium tuberculosis infection is initiated by the inhalation and implantation of bacteria in the lung alveoli, where they are phagocytosed by macrophages. Even a single bacterium may be sufficient to initiate infection. Thereafter, the clinical outc ...

AMER SOC MICROBIOLOGY2022

Exploring the mechanisms governing nuclear cGAS localization and activity

Marilena Wischnewski

Recognition of pathogen-derived molecules through germline-encoded receptors is a fundamental principle of innate immunity. Pattern recognition receptors detect specific intracellular danger signals to trigger potent immune responses. The DNA sensor cyclic ...

EPFL2022

Fluorescent D-Amino Acids for Super-resolution Microscopy of the Bacterial Cell Wall

Mischa André Meyer, Faustine Ambroisine Charline Ryckebusch, Suliana Manley, Luc Reymond, Chen Zhang, Juliette Griffie, Willi Leopold Stepp, Ophélie Rutschmann, Jiangtao Qiao

Fluorescent D-amino acids (FDAAs) have previ-ously been developed to enable in situ highlighting of locations of bacterial cell wall growth. Most bacterial cells lie at the edge of the diffraction limit of visible light; thus, resolving the precise details ...

2022

The human telomeric proteome during telomere replication

Chih-Yi Gabriela Lin, Joachim Lingner, Aleksandra Vancevska, Thomas Frédéric Lunardi, Gérald Joseph Paul Lossaint

Telomere shortening can cause detrimental diseases and contribute to aging. It occurs due to the end replication problem in cells lacking telomerase. Furthermore, recent studies revealed that telomere shortening can be attributed to difficulties of the sem ...

OXFORD UNIV PRESS2021

Challenging endings: How telomeres prevent fragility

Joachim Lingner, Galina Glousker

It has become apparent that difficulties to replicate telomeres concern not only the very ends of eukaryotic chromosomes. The challenges already start when the replication fork enters the telomeric repeats. The obstacles encountered consist mainly of nonca ...

WILEY2021

Dynamic Chromatin Invasion and Remodeling by the Transcription Factor Rap1

Maxime Nicolas Mivelaz

Pioneer transcription factors (PTF) are a subset of transcription factors with nucleosome-binding properties allowing them to bind specific sequences in condensed chromatin. Although the biological functions of PTFs including target genes and epigenetic ch ...

EPFL2021

Chromatin Proteomics to Study Epigenetics - Challenges and Opportunities

Guido Van Mierlo

Regulation of gene expression is essential for the functioning of all eukaryotic organisms. Understanding gene expression regulation requires determining which proteins interact with regulatory elements in chromatin. MS-based analysis of chromatin has emer ...

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC2021

Multiplexed Single-Molecule Experiments Reveal Nucleosome Invasion Dynamics of the Cas9 Genome Editor

Beat Fierz, Louise Catherine Bryan, Kristina Makasheva

Single-molecule measurements provide detailed mechanistic insights into molecular processes, for example in genome regulation where DNA access is controlled by nucleosomes and the chromatin machinery. However, real-time single-molecule observations of nucl ...

AMER CHEMICAL SOC2021