Recessive Loss of DIAPH1 Function Causes a Progressive Neurodevelopmental Syndrome with Variable Immunological Involvement

Biallelic DIAPH1 pathogenic variants cause a neurodevelopmental syndrome occasionally associated with immunodeficiency. This study aims to define the clinical and immunological spectrum of DIAPH1-rela...

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IFI16 senses and protects stalled replication forks

Gamble et al. demonstrate that detection of stalled replication forks by the innate immune sensor IFI16 induces an early STING-dependent pro-inflammatory cytokine response independently of cGAS and DNA damage. Furthermore, IFI16 exhibits dual functionality during replication stress by protecting stalled, remodeled replication forks from nucleolytic degradation.

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Loss of CTLH component MAEA impairs DNA repair and replication and leads to developmental delay - EMBO Molecular Medicine

Ubiquitin E3 ligases play crucial roles in the DNA damage response (DDR) by modulating the turnover, localization, activation, and interactions of DDR and DNA replication proteins. We performed a CRIS...

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How DNA secondary structures drive replication fork instability

DNA secondary structures, such as hairpins, cruciforms, triplexes, G-quadruplexes and iMotifs, are common, dynamic features that replication forks rou…

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Cohesin drives chromatin scanning during the RAD51-mediated homology search

Cohesin folds genomes into chromatin loops, the roles of which are under debate. We found that double-strand breaks (DSBs) induce de novo formation of chromatin loops in human cells, with the loop bas...

science.org

Senior Research Technician at University of Birmingham

An academic position as a Senior Research Technician is being advertised on jobs.ac.uk. Click now to find more details and explore additional academic job opportunities.

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Transcriptional repression facilitates RNA:DNA hybrid accumulation at DNA double-strand breaks | Nature Cell Biology

RNA:DNA hybrids accumulate at DNA double-strand breaks (DSBs) and were shown to regulate homologous recombination repair. The mechanism responsible for the formation of these non-canonical RNA:DNA structures remains unclear although they were proposed to arise consequently to RNA polymerase II or III loading followed by DSB-induced de novo transcription at the break site. Here, we found no evidence of RNA polymerase recruitment at DSBs. Rather, strand-specific R-loop mapping revealed that RNA:DNA hybrids are mainly generated at DSBs occurring in transcribing loci, from the hybridization of pre-existing RNA to the 3′ overhang left by DNA end resection. We further identified the H3K4me3 reader spindlin 1 and the transcriptional regulator PAF1 as factors promoting RNA:DNA hybrid accumulation at DSBs, through their role in mediating transcriptional repression in cis to DSBs. Altogether, we provide evidence that RNA:DNA hybrids accumulate at DSBs occurring in transcribing loci as a result o

doi.org

A nuclease-driven mechanism of post-replicative ssDNA gap suppression.

The persistence of post-replicative ssDNA gaps following PRIMPOL-mediated replication repriming is linked to chemosensitivity, and in all models reported to date the nuclease MRE11 has been implicated...

biorxiv.org

DDIAS is a single-stranded DNA-binding effector of the TOPBP1-CIP2A complex in mitosis

DNA double-strand breaks and unresolved DNA replication intermediates are particularly dangerous during mitosis. Paradoxically, cells inactivate canonical DNA repair mechanisms during chromosome segre...

biorxiv.org

The DNA replication machinery transmits dual signals to prevent unscheduled licensing and execution of centrosome duplication - Nature Communications

Cell division requires strict control of DNA replication and centrosome duplication. Here, the authors reveal that DNA replication machinery transmits dual signals to control proper timing of centroso...

nature.com

The RING finger E3 ligase RNF25 protects DNA replication forks independently of its canonical roles in ubiquitin signaling - Nature Communications

DNA replication stress is a driver of genome instability. Here, the authors identify a role of the E3 ligase RNF25 in promoting replication stress tolerance. Mechanistically, RNF25 recruits the fork p...

nature.com

USP1/UAF1 targets polyubiquitinated PCNA with an exo-cleavage mechanism that can temporarily enrich for monoubiquitinated PCNA - Nature Communications

DNA damage tolerance is regulated by ubiquitination of PCNA. Here, the authors present kinetic and structural studies showing that USP1/UAF1 prefers trimming K63- and K48-ubiquitin chains down over cl...

doi.org

The DNA replication checkpoint limits Okazaki fragment accumulation to protect and restart stalled forks

Canal et al. used biochemical reconstitution of DNA replication to show that continued Okazaki fragment synthesis after nucleotide exhaustion depletes PCNA, RFC, and DNA polymerases ε and δ, deprotecting replication forks and impairing restart. By limiting Okazaki fragment generation and factor depletion, the replication checkpoint protects forks, allows restart, and promotes survival.

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Home - Birmingham Centre for Genome Biology 2025

BCGB 2025, Birmingham Centre for Genome Biology Conference 2025

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Postdoctoral Research Associate in the Blackford Group

A position as Postdoctoral Research Associate is available at the Department of Cellular and Molecular Medicine, in the group headed by Dr. Andrew Blackford. Th

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USP37 prevents premature disassembly of stressed replisomes by TRAIP - Nature Communications

The replicative helicase CMG is targeted for removal or proteolysis by the E3 ubiquitin ligase TRAIP. This study describes how the de-ubiquitylating enzyme USP37 protects genome stability by preventin...

nature.com

BRCA2 C-terminal clamp restructures RAD51 dimers to bind B-DNA for replication fork stability

With detailed structural and molecular analyses, Longo et al. find that the BRCA2 C-terminal TR2, which is a critical cancer therapy resistance factor, reshapes the RAD51 dimer for B-DNA binding that is incompatible with double-strand break repair interactions but activates it in DNA replication fork protection.

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USP37 protects mammalian cells during DNA replication stress by counteracting CUL2LRR1 and TRAIP

Villa et al. show that the USP37 deubiquitylase is tethered to the CMG helicase at DNA replication forks in mammalian cells. USP37 protects cells during DNA replication stress by counteracting two replisome-coupled ubiquitin ligases. USP37 counteracts CUL2LRR1 during DNA synthesis defects and opposes TRAIP in response to topological stress.

dlvr.it

ARID1A stabilises non-homologous end joining factors at DNA breaks induced by the G4 ligand pyridostatin

ARID1A is a subunit of the BAF chromatin remodelling complex that is frequently mutated in cancer. It is challenging to predict how ARID1A loss impacts cancer therapy response because it participates ...

biorxiv.org

Parp1 deletion rescues cerebellar hypotrophy in xrcc1 mutant zebrafish - Scientific Reports

Scientific Reports - Parp1 deletion rescues cerebellar hypotrophy in xrcc1 mutant zebrafish

nature.com

Inherited deficiency of DIAPH1 identifies a DNA double strand break repair pathway regulated by γ-actin - Nature Communications

DNA double strand break repair pathways ensure genome stability and prevent disease. Here the authors show that the actin nucleating factor DIAPH1 and γ-actin promote homologous recombination (HR)-dep...

nature.com

53BP1/RIF1 and DNA-PKcs show distinct genetic interactions with diverse chromosomal break repair outcomes.

DNA double strand breaks (DSBs) are the effective lesion of cancer radiotherapy and induce gene editing. 53BP1 accumulates at DSBs and is implicated in end joining (EJ) repair, but its influence on DS...

biorxiv.org

JCI - Genetic inactivation of FAAP100 causes Fanconi anemia due to disruption of the monoubiquitin ligase core complex

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