DNA repair and human disease

Methyl-based NMR experiments on P. furiosus MR reveal multiple DNA-bound conformations that cooperate to initiate the repair of DNA double-stranded breaks, highlighting the dynamic conformational coordination in DNA repair.

Interaction between BLM and condensin II regulates replication dynamics and promotes mitotic chromosome stability, while contributing to DNA break repair and facilitating BLM localization to nascent DNA.

Early T. gondii infection induces host S-phase arrest and DNA breaks, with binucleation and micronuclei formation observed by 3 h p.i., indicating genomic instability. DNA damage was MYR1-dependent and ROS-independent, compromising host DNA integrity post-infection.

Reversed forks must be protected from uncontrolled nucleolytic degradation. Xie et al. reveal a collaborative defense mechanism orchestrated by Myb/SANT-like DNA-binding domain-containing protein 4 and the breast cancer susceptibility proteins (BRCA1/2)–DNA repair protein RAD51 pathway, which synergistically preserve the integrity of reversed forks.

Here, Zerio et al. use cryo-electron microscopy to show how the helicase domain of DNA polymerase θ aligns broken DNA strands by matching short sequences, a process linked to cancer. These findings may guide future therapies targeting error-prone DNA repair.

Here, using mouse genetics, biochemistry and cell-based experiments, the authors reveal that shieldin primarily catalyzes DNA priming and polymerase-dependent fill-in synthesis at 5′ recessed DNA ends during the joining of activation-induced cytidine deaminase-dependent DNA breaks.

What is the role of disorder in non-homologous end-joining proteins? The authors use nuclear magnetic resonance to reveal that disordered regions mediate a network of multivalent interactions, promoting biomolecular condensation that accelerates DNA ligation kinetics.

Here the authors show that the nucleus undergoes a transient ‘metamorphosis’ within a nuclear–cytoplasmic DNA damage response linked to health and disease. Through this process, the nuclear envelope projects tubules that capture damaged DNA, mediating its repair.