Distinct ATRX functions cooperate with 9-1-1 and CST complexes to safeguard replication and telomere integrity - Nature Structural & Molecular Biology

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...

nature.com

PARP1 trapping activates ATM-mediated NF-κB signaling independent of replication in response to TOP1 blockade

Abstract. The NF-κB signaling pathway is a key driver of inflammation and can be activated by many genotoxic stresses. Yet, the mechanisms by which differe

doi.org

No Time to Fold: Intrinsically Disordered Microproteins in Action

Advances in genomics, proteomics, and bioinformatics have uncovered the existence of thousands of translated small open reading frames less than 100–150 codons in length that encode microproteins. In ...

pubs.acs.org

A dynamic search mechanism enables APE1 to identify AP-sites in DNA

Abstract. Apurinic/apyrimidinic (AP) sites are among the most frequent DNA lesions, arising thousands of times per cell each day. These lesions threaten ge

academic.oup.com

Endogenous Sources of Abasic Sites and Implications for DNA Replication: Mechanisms of Fork Stalling and Recovery

Apurinic/apyrimidinic (AP) sites, also known as abasic sites, are among the most frequent DNA lesions, arising spontaneously or as intermediates in base excision repair. Their structural impediment to...

annualreviews.org

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Replicative gaps in DNA damage tolerance, genome instability, and cancer therapy

Replicative single-stranded DNA gaps arise when DNA synthesis proceeds past lesions or difficult-to-replicate regions. This review delineates the pathways that generate, stabilize, and process these i...

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biorxiv.org

A small polymerase ribozyme that can synthesize itself and its complementary strand

The emergence of a chemical system capable of self-replication and evolution is a critical event in the origin of life. RNA polymerase ribozymes can replicate RNA, but their large size and structural ...

science.org

FANCD2 restrains fork progression and prevents fragility at early origins upon re-replication - Nature Communications

Re-replication is a driving force of tumorigenesis and genomic instability. Here, the authors show that upon re-replication, FANCD2 localizes at early origins to limit replisome progression, ssDNA gap...

nature.com

Nucleoplasmic Lamin A/C controls replication fork restart upon stress by modulating local H3K9me3 and ADP-ribosylation levels

Nature Communications - Replication fork plasticity upon genotoxic stress is modulated by nuclear architectural components by elusive mechanisms. Here the authors implicate Lamin A/C – best...

rdcu.be

A recurrent pathogenic BRCA2 truncating variant reveals a role for BRCA2-PCAF complex in modulating NF-κB-driven transcription - Nature Communications

Pathogenic BRCA2 truncating variants in heterozygosis drive distinct cancer-linked mechanisms. Here the authors show that one causes PARPi sensitivity and HR loss via haploinsufficiency, while another...

nature.com

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

Circadian regulation of homologous recombination by cryptochrome1-mediated dampening of DNA end resection

Nature Communications - The study shows that DNA double-strand break repair follows a circadian rhythm: homologous recombination peaks in the morning and declines by evening. CRY1 regulates CCAR2...

rdcu.be

H263A and SCAN1/H493R mutant TDP1 block TOP1-induced double-strand break repair during gene transcription in quiescent cells and promote cell death

Cell Death & Disease - H263A and SCAN1/H493R mutant TDP1 block TOP1-induced double-strand break repair during gene transcription in quiescent cells and promote cell death

rdcu.be

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

Saur, Lesage et al. report that RNA:DNA hybrids arise at double-strand breaks in transcribed genes, independently of de novo recruitment of RNA polymerase II/III, as a result of DSB-induced transcript...

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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

Mitotic single-stranded DNA suppression by DDIAS

Incomplete DNA replication and chromosome breakage during mitosis pose major threats to chromosome segregation. The CIP2A-TOPBP1 complex acts to mitigate this peril, but its exact role is not yet unde...

biorxiv.org

NASP modulates histone turnover to drive PARP inhibitor resistance - Nature

PARP inhibitor treatment triggers histone release from the chromatin in cancer cells; consequently, targeting the histone chaperone NASP renders cells vulnerable to PARP inhibition.

nature.com

DNA-repair-driven cell death compels us to rethink cancer therapies - Nature Reviews Molecular Cell Biology

Emerging evidence suggests that, following genotoxic therapy, it is the repair of DNA double-strand breaks, rather than the damage itself, that frequently drives cancer cell death.

nature.com