Adenosine triphosphate (ATP)–dependent chromatin remodeling enzymes mobilize nucleosomes, but how such mobilization affects chromatin condensation is unclear. We investigate effects of two major remod...

Synthetic lethality describes a genetic relationship where the loss of two genes results in cell death, but the loss of one of those genes does not. Drugs used for precision oncology can exploit synth...

Homologous recombination (HR) is a DNA double-strand break repair pathway that facilitates genetic exchange and protects damaged replication forks during DNA synthesis. As a template-based repair proc...

Nature Communications - Determining how replication forks move across the human genome is critical for the effective use of agents that target replication stress. Here, the authors present...

We are in the process of inviting a number of outstanding Australian leaders in the fields of DNA repair, Cell Cycle and Telomere biology. Current invited speakers include: Lisa Alcock, Curtain Uni…

Many protein–protein interactions depend on Short Linear Motifs (SLiMs). In this study, the authors use large-scale binding assays, deep mutational scanning, and structural analysis to map SLiMs recog...

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.

October 20-22, 2025

Deltex E3s modify ADP-ribosylated targets with ubiquitin, creating a hybrid modification whose readers remains unknown. Here, the authors synthesise a non-hydrolysable probe that mimics the modificati...

DNA end resection to generate 3' ssDNA overhangs is the first step in homology-directed mechanisms of double-strand break (DSB) repair. While end resection has been extensively studied in the repair of endonuclease-induced DSBs, little is known about how resection proceeds at DSBs generated during DNA replication. We previously established a system to generate replication-dependent double-ended DSBs at the sites of nicks induced by the Cas9D10A nickase in the budding yeast genome. Here, we suggest that these DSBs form in an asymmetric manner, with one break end being blunt or near blunt, and the other bearing a 3' ssDNA overhang of up the size of an Okazaki fragment. We find that Mre11 preferentially binds blunt ends and is required for the removal Ku from these DSB ends. In contrast, the ends predicted to have 3' overhangs have minimal Ku binding, and end resection at these break ends can proceed in a mostly Mre11-independent manner through either the Exo1 or Dna2-Sgs1 long-range resection pathways. These findings indicate that resection proceeds differently at replication-dependent DSBs than at canonical DSBs, and reveals that Ku selectively binds nearly blunt ends, potentially explaining why replication-dependent DSBs are poorly repaired by non-homologous end joining. ### Competing Interest Statement The authors have declared no competing interest. National Institute of General Medical Sciences, https://ror.org/04q48ey07, R35GM126997

FANCM–RMI is a protein–protein interaction that maintains genome stability during DNA repair events in cancers that rely on the Alternative Lengthening of Telomeres (ALT) pathway for survival. We repo...

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 ...

imageimageFANCM employs a sophisticated dual recognition mechanism in genome maintenance, using distinct DNA-binding domains to identify and move around on branched DNA structures. This study reveals how FANCM evolved from an ancient repair motor ...