Segura-Bayona et al. uncover genetically separable ATRX functions that independently safeguard telomeres and genome replication, revealing how CST and 9-1-1 pathways suppress accumulation of toxic sin...

Often mutated in cancer, the ATRX gene helps cells copy their DNA without damage. Crick scientists have uncovered new functions that leave ATRX-deficient cancer cells vulnerable.

Telomeres are nucleoprotein elements bound by shelterin that protect chromosome ends from DNA damage signalling and inappropriate repair. A defining architectural feature is the telomere loop (t-loop)...

Telomerase counteracts telomere shortening by repeatedly adding DNA repeats to chromosome ends. We identified the replication protein A (RPA) heterotrimer as a telomerase processivity factor critical ...

Homologous recombination (HR) deficiency upon Breast Cancer Gene 2 (BRCA2) loss arises from defects in the formation of RAD51 nucleoprotein filaments. We demonstrate that loss of the anti-recombinase ...

Analysis of the longest-lived mammal, the bowhead whale, reveals an improved ability to repair DNA breaks, mediated by high levels of cold-inducible RNA-binding protein.  &nbs...

Mutations in the ATRX chromatin remodeller predispose to a developmental genetic disorder and cancer, but how it safeguards genome and telomere stability remains unresolved. Here, we uncover critical ...

The tRNA nuclease SLFN11 is epigenetically silenced in ~50% of treatment-naive tumours and is the strongest predictor of chemoresistance but why it is frequently inactivated in cancer is unknown. To a...

Certain antimetabolites used to treat cancer are more neurotoxic than others, and it is now shown that this is due to their greater tendency to generate DNA double-stranded breaks, whereas less n...

G-quadruplexes (G4s) are prevalent DNA structures that regulate transcription but also threaten genome stability. How G4 dynamics are controlled remains poorly understood. Here, we report that RNA tra...

A multigenerational single-cell tracking approach provides a framework to dissect phenotypic plasticity at the single-cell level, offering insights into cellular processes that may resemble early even...

Nature - Ku limits RNA-induced innate immunity to allow Alu-expansion in primates

Background For decades, vast stretches of the genome were dismissed as non-functional ‘junk’. However, our group and others have revealed that these regions harbor numerous non-canonical open reading ...

DNA G-quadruplexes (G4s) are non–B-form DNA secondary structures that threaten genome stability by impeding DNA replication. To elucidate how G4s induce replication fork arrest, we characterized fork ...

Losing parental histones during DNA replication fork passage challenges differentiation competence and cell viability.

SCF–FBXO31 scans proteins for C-terminal amidation and marks them for subsequent proteasomal degradation.

Szmyd et al. show that DNA repair pathways impact whether cells with DNA lesions arrest in mitosis. The formation of homologous recombination-driven double Holliday junctions elicits mitotic cell deat...

Cacioppo, Gillis, Shlamovitz, Zeller, et al. show that CRL3ARMC5 ubiquitylates RNA Pol II at early stages of transcription as part of a major homeostatic RNA Pol II turnover mechanism. CRL3ARMC5 and the Integrator phosphatase act as complementary pathways, monitoring the quantity and quality of RNA Pol II complexes before they are licensed into elongation.

Nature - The molecular mechanisms of how small changes in the degree of inclusion of a neuron-specific microexon in CPEB4 lead to dominant-negative effects in the expression of genes associated...

Telomere dysfunction, usually owing to shortening, activates cellular senescence and can contribute to age-associated diseases and cancer. Mouse models are crucial for telomere research, but human and...