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...

The FANCD2-FANCI heterodimer contributes to DNA repair at interstrand crosslinks and sites of replication stress. This complex has been physically and mechanistically linked to double-strand break (DSB) repair, but its role in that process remains undefined. Here we show that the FANCD2-FANCI heterodimer dynamically interacts with open chromatin regions, including transient, DSB-induced open chromatin, where it can be stabilized by co-activation by the DNA repair kinase ATM and the Fanconi anemia core ubiquitin ligase. The loaded FANCD2-FANCI heterodimer stabilizes open chromatin and promotes resection and loading of RPA through increased association of BRCA1 and BLM. Chromatin-loaded FANCD2-FANCI has a second distinct function promoting a G2 arrest that is dependent on the ATR-CHK1-WEE1 axis. Our results support a two-step genome surveillance model in which FANCD2-FANCI monitors open chromatin sites and is stably loaded to coordinate DNA repair activities in response to signaling from a DNA repair kinase. ### Competing Interest Statement The authors have declared no competing interest.

Your group The Cortes-Ciriano group studies the mutational processes and mechanisms of genome instability underpinning tumourigenesis, immune escape, and drug response through the analysis of high-thr...

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

Nature Cancer - Whalen et al. report that increased DNA end resection in BRCA-deficient, PARP inhibitor-resistant cancers leads to increased sensitivity to DNA nicks, limiting tumor formation in...

DNA double strand breaks (DSBs) are widely considered the most cytotoxic DNA lesions occurring in cells because they physically disrupt the connectivity of the DNA double helix. Homologous recombinati...

Hervé, Scelfo et al. show that chromosome mis-segregation induces mTORC2- and ATR-mediated p53 activation through a mechanosensitive checkpoint at the nuclear envelope triggered by altered heterochrom...

Large extrachromosomal DNAs are engineered using a CRISPR- and Cre–loxP-based approach and shown to drive cancer in mouse models, with potential applications in determining the role of oncogene a...

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The experience with PARP inhibitors provides evidence of the clinical utility of synthetic lethality, whereby the simultaneous presence of two specific alterations is required for antitumour activity....

Nature Communications - DNA repeats can lengthen or shorten during their replication, which may lead to a human disease. Here, the authors discovered that an essential replication protein, Mcm10,...

When cells enter mitosis with under-replicated DNA, sister chromosome segregation is compromised, wh

Using single-cell DNA sequencing we show that most healthy women harbour rare populations of aneuploid epithelial cells with copy number alteration events in their breast tissue that expand and accumu...