CIP2A tetramerization is required for mitotic DNA repair

DNA lesions that persist in mitosis threaten genome stability. These lesions recruit TOPBP1-CIP2A, a complex crucial to tether and process damaged DNA on mitotic chromosomes. Importantly, CIP2A is syn...

biorxiv.org

A versatile cGAMP reporter reveals principles of cGAS activation by DNA damage and chromosome instability - Nature Cell Biology

Lebrec et al. present a FRET-based cGAS reporter and show that cGAS activation by genotoxic stress is rare and uncoupled from micronuclei. The study implicates R-loop structures and subtypes of chroma...

nature.com

Structural mechanism of TOPBP1 activating the ATR–ATRIP replication checkpoint kinase - Nature Structural & Molecular Biology

Li et al. present cryo-EM structures of the ATR–ATRIP complex bound to the ATR-activating domains of TOPBP1 and ETAA1; these reveal distinct binding modes and allosteric mechanism of activation for TO...

nature.com

A breakage–replication/fusion process explains complex rearrangements and segmental DNA amplification - Nature Genetics

This paper introduces breakage–replication/fusion, a genomic rearrangement process underpinning three patterns of copy-number gains found in cancer and other diseases.

nature.com

Rescuing the bacterial replisome at a nick requires recombinational repair and helicase reloading - Nature Communications

DNA damage can lead to cell death. Here, the authors show that a simple cut on either strand of DNA can inactivate bacterial chromosome replication. Surprisingly, only a core set of recombination prot...

nature.com

Engineered chromatin readers track damaged chromatin dynamics in live cells and animals - Nature Communications

DNA damage threatens genome stability, but its dynamics in living systems remain difficult to track. Here, the authors engineer MCPH1-based protein probes that specifically recognize γH2AX, enabling r...

nature.com

Proteome-wide in silico screening for human protein-protein interactions

Protein-protein interactions (PPIs) drive virtually all biological processes, yet most PPIs have not been identified and even more remain structurally unresolved. We developed a two-step computational...

biorxiv.org

PhD student DNA repair in kidney cancer | Werken bij UMC Groningen

werkenbijumcg.nl

Mutational signature catalogue (MUSIC) of DNA double-strand break repair

Genome alterations arise from inaccurate DNA repair, accumulating into distinct mutational signatures. Here, we investigate the role of every genomically encoded gene in double-strand break (DSB) repa...

biorxiv.org

CIP2A is required for mitotic recruitment of the SLX1/XPF/MUS81 tri-nuclease complex to replication stress-induced DNA lesions to maintain genome integrity

Perturbed DNA replication can lead to incompletely replicated DNA when cells enter mitosis and can interfere with chromosome segregation. Cells therefore require mechanisms to resolve these lesions du...

biorxiv.org

REV7 functions with REV3 as a checkpoint protein delaying mitotic entry until DNA replication is completed

How cells ensure that they enter mitosis after completing replication of their genome is not fully resolved. Sobkowiak et al. describe a checkpoint involving REV7. This checkpoint has mechanistic similarities to the spindle anaphase checkpoint mediated by…

dlvr.it

A CPC-shelterin-BTR axis regulates mitotic telomere deprotection - Nature Communications

Here the authors reveal how telomeres signal mitotic stress. A key protein network alters their structure exposing telomere ends to signal mitotic stress, ultimately triggering a controlled DNA damage...

nature.com

WEE1 inhibitors trigger GCN2-mediated activation of the integrated stress response

The WEE1 kinase negatively regulates CDK1/2 to control DNA replication and mitotic entry. Genetic factors that determine sensitivity to WEE1 inhibitors (WEE1i) are largely unknown. A genome-wide inser...

biorxiv.org

The transcriptomic architecture of common cancers reflects synthetic lethal interactions - Nature Genetics

Tumor cells upregulate compensatory buffering genes following tumor suppressor loss. These genes may represent new synthetic lethal partners that could be harnessed therapeutically.

nature.com

DNA replication and genome maintenance: from basic biology to disease

embl.org

Predictomes, a classifier-curated database of AlphaFold-modeled protein-protein interactions

Schmid and Walter train a classifier that discerns functionally relevant structure predictions in proteome-wide protein-protein interaction (PPI) screens using AlphaFold-Multimer, and they use this co...

cell.com

Professorship in genetics and molecular cell biology (W3) (f/m/d) - Academic Positions

The University of Cologne is one of the oldest and largest universities in Germany. With its six Faculties covering a broad spectrum of disciplines and its i...

academicpositions.com

Spatial mapping of DNA synthesis reveals dynamics and geometry of human replication nanostructures

DNA replication is essential to life and ensures the accurate transmission of genetic information, which is significantly disturbed during cancer development and chemotherapy. While DNA replication is...

biorxiv.org

Mitotic transcription ensures ecDNA inheritance through chromosomal tethering

Extrachromosomal DNA (ecDNA) are circular DNA bodies that play critical roles in tumor progression and treatment resistance by amplifying oncogenes across a wide range of cancer types. ecDNA lack cent...

biorxiv.org