Genomic instability

Two new papers in Nature report copy-number-based classification systems across cancer types that provide routes for personalized therapy.

In this Journal Club article, Geoff Faulkner discusses how a ground-breaking study of LINE-1 mobility in human genomes demonstrated not just a role in disease but also molecular details of the mechanisms of retrotransposition.

The collapse of DNA replication forks leads to the formation of single-ended DNA double-strand breaks. One would have assumed that these breaks would be repaired as soon as possible. However, a recent study suggests that a delay in DNA polymerase θ-mediated end joining until mitosis, orchestrated by BRCA2 and RAD52, favors genomic stability.

Are your mouse colonies in the best state to resume experiments? A short commentary on some key issues to consider when moving forward.

Schep et al. show that non-homologous end joining is strongly favoured in euchromatin, whereas single-stranded template repair is moderately preferred in heterochromatin. Importantly, heterochromatin features that promote microhomology-mediated end joining also decrease Cas9 efficiency.

Chromosomal instability (CIN) is a hallmark of malignant evolution that underpins cancer progression and therapeutic evasion. There are few established experimental systems to study CIN and ultimately develop potential therapeutic options. A new study now identifies the MSL chromatin complex as a potential vulnerability against CIN in cancer cells.