Faithful DNA replication is essential for genome stability, yet replication forks face constant stress. The Bloom syndrome helicase (BLM) safeguards fork integrity, but excessive BLM activity can itse...

Alternative polyadenylation (APA) generates transcript isoforms with variable 3′ untranslated regions (UTR) lengths, yet its role in DNA damage respon…

The analysis of DNA sequence outcomes provides molecular insights into double-strand break (DSB) repair mechanisms. Using parallel in-pool profiling of Cas9-induced insertions and deletions (indels) w...

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...

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...

Cyclin-dependent kinases (CDKs) are prototypical regulators of the cell cycle. The CDK-activating kinase (CAK) acts as a master regulator of CDK activity by catalyzing the activating phosphorylation o...

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 ...

Efficient eukaryotic DNA replication relies on the coordinated actions of replicative and error-prone polymerases, with the latter providing flexibility at the cost of mutagenesis. DNA polymerase η (P...

Cohesin loop extrusion is a major driver of chromosome folding, but how its dynamics are controlled to shape the genome remains elusive. Here we disentangle the contributions of the cohesin cofactors ...

DNA2 suppresses recombination-restarted replication and checkpoint activation at stalled forks, and its loss triggers recombination-dependent synthesis, checkpoint signalling and cell-cycle exit, high...

Research in the DNA replication field is progressing at a remarkable rate. Technological innovations in biochemical reconstitution, structural biology, proteomics and DNA sequencing are helping to rap...

Nature Reviews Molecular Cell Biology - Changes in nuclear and genome organization promote the repair of DNA double-strand breaks and genome stability. Processes that are involved include the...

Replication fork collapse at single-strand DNA breaks (SSBs) poses a serious threat to genome stability. Using Xenopus egg extracts, we show that a replication fork encountering an SSB on either the l...

Abstract. Cell cycle checkpoints are the regulatory mechanisms that secure the strict order of cellular events for cell division that ensure genome integri

imageimageHypoxia contributes to cancer resistance to both standard therapies and immunotherapy. This work demonstrates that tumor hypoxia promotes immune evasion by autophagy-mediated downregulation ...

Using unbiased CRISPR-Cas9-based genetic screens, Joseph et al. identify MAPK14/p38α as a dependency and vulnerability of high-grade endometrial cancer (HGEC) metastatic spheroids. MAPK14/p38α critically programs the phosphoproteome, transcriptome, and metabolome of HGEC spheroids, promoting cancer stemness and tumorigenicity.

Abstract. DNA replication faces challenges from DNA lesions originated from endogenous or exogenous sources of stress, leading to the accumulation of singl

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DNA–protein crosslinks (DPCs) are highly toxic DNA lesions that are relevant to multiple human diseases. They are caused by various endogenous and environmental agents, and from the actions of enzymes...

Here the authors identify PCNA, a master regulator of DNA replication, as a ubiquitin substrate for the BRCA1/BARD1 heterodimer. This modification is crucial to avoid the appearance of unreplicated DN...

Together with structural analyses, a cell-free system for transcription-coupled nucleotide excision repair (TC-NER) shows that STK19 is an integral component of the TC-NER complex that couples RNA pol...

Dreyer et al. show the broad and rapid impact that acute inhibition of chromatin formation in S-phase has on DNA replication, chromatin stability, and cell-cycle progression. This study sheds light on...

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Abstract. RNF168 orchestrates a ubiquitin-dependent DNA damage response to regulate the recruitment of repair factors, such as 53BP1 to DNA double-strand b